Lifescience Knowledge Center

Whole transcriptome sequencing services for cancer

Thu, 06 Apr 2023 09:33:57 GMT

Cancer WTS

mRNA Sequencing

Small RNA Sequencing

CircRNA Sequencing

LncRNA Sequencing

Exosome RNA Sequencing

Ultra Low Input RNA Sequencing

RNA Sequencing for Formalin-Fixed Paraffin-Embedded (FFPE) Tissue

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Whole transcriptome sequencing for cancer

Thu, 06 Apr 2023 09:33:24 GMT

Advances in massive parallel DNA sequencing technologies have enabled RNA-seq by sequencing of cDNA. RNA-seq is a revolutionary tool with better resolution and higher reproducibility that offers many advantages over the traditional microarray technologies. RNA-seq can be used to extend our knowledge of alternative splicing events, novel genes and transcripts, and fusion transcripts. RNA-seq can also help to understand molecular mechanisms and then it tells about signaling pathways which controls embryonic development. The transcriptome data give researchers a good place to start searching for a newly found gene's function.

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Cancer whole transcriptome sequencing services

Thu, 06 Apr 2023 09:32:50 GMT

RNA-seq is a revolutionary tool with better resolution and higher reproducibility that offers many advantages over the traditional microarray technologies. RNA-seq can be used to extend our knowledge of alternative splicing events, novel genes and transcripts, and fusion transcripts. RNA-seq can also help to understand molecular mechanisms and then it tells about signaling pathways which controls embryonic development. The transcriptome data give researchers a good place to start searching for a newly found gene's function.

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Transcriptome sequencing for cancer

Thu, 06 Apr 2023 09:32:17 GMT

The transcriptome is the entire set of RNA transcripts in a given cell for a specific developmental stage or physiological condition. RNA is a polymeric molecule implicated in various biological processes, such as the coding, decoding, regulation, and expression of genes. RNA molecules include mRNAs, long non-coding RNA (lncRNAs), circular RNA (circRNAs), microRNA (miRNA), message RNA (mRNA), transfer (tRNA) and ribosomal ribonucleic acid (rRNA).

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RNA services for cancer

Thu, 06 Apr 2023 09:31:47 GMT

RNA-seq is an important tool for interpreting the functional elements of the genome as well as for understanding the underlying mechanisms of diverse diseases, especially cancers.

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WTS services for cancer

Thu, 06 Apr 2023 09:31:24 GMT

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WTS for cancer

Thu, 06 Apr 2023 09:30:56 GMT

Whole transcriptome sequencing (WTS) is used to reveal the presence and quantity of RNA, in a biological sample under specific conditions.

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RNA-seq for cancer

Thu, 06 Apr 2023 09:30:32 GMT

Whole transcriptome analysis has been an important tool in solving biological issues and understanding the molecular mechanisms of many diseases including human cancers.

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Cancer WTS services

Thu, 06 Apr 2023 09:29:29 GMT

Whole transcriptome analysis has been an important tool in solving biological issues and understanding the molecular mechanisms of many diseases including human cancers. Whole transcriptome sequencing (WTS) is used to reveal the presence and quantity of RNA, in a biological sample under specific conditions.

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Whole genome sequencing services for cancer

Thu, 06 Apr 2023 09:28:53 GMT

Researchers have found that DNA variations outside the exons can affect gene activity and protein production and lead to genetic disorders--variations that whole exome sequencing would miss. https://www.creative-biolabs.com/suprecision/whole-genome-sequencing-service-for-cancer.htm

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NGS data analysis services for oncology

Mon, 06 Mar 2023 09:57:39 GMT

Highly accurate interpretation

Rapid and comprehensive discovery

Accurate results associated with the deep coverage

Flexibility to meet every unique client’s need

Highly seasoned bioinformatics specialists

Easy to understand for non-professionals

Secured and long-term secure cloud storage

Time-saving and price favorable

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Bioinformatic services for oncology

Mon, 06 Mar 2023 09:57:17 GMT

The genetic variants analysis pipeline consists of 1) quality control of raw data, 2) production of the clean data, 3) unspliced mapping of the clean data onto a reference genome, 4) post-alignment processing, 5) quality control of the mapped reads, 6) variant calling, annotation and prioritization.

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Bioinformatic solutions for oncology

Mon, 06 Mar 2023 09:56:43 GMT

The emergence of NGS platforms imposes increasing demands on statistical methods and bioinformatic tools for the analysis and the management of the huge amounts of data. NGS technologies have progressive advantages in terms of cost-effectiveness, unprecedented sequencing speed, high resolution and accuracy in genomic analyses, thus are playing an increasingly important role in fields of oncology and immunology. The combined power of NGS and bioinformatics analysis is vital for diagnostics and medical treatment.

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Bioinformatic platform for oncology

Mon, 06 Mar 2023 09:56:28 GMT

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Bioinformatic analysis for oncology

Mon, 06 Mar 2023 09:56:02 GMT

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Bioinformatic services for cancer

Mon, 06 Mar 2023 09:55:42 GMT

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Bioinformatic solutions for cancer

Mon, 06 Mar 2023 09:55:25 GMT

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Bioinformatic platform for cancer

Mon, 06 Mar 2023 09:55:01 GMT

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Bioinformatics Analysis is Urgently Needed

Mon, 06 Mar 2023 09:54:29 GMT

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Bioinformatics Analysis Service

Mon, 06 Mar 2023 09:54:10 GMT

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Whole Exome Sequencing (WES) Bioinformatic Analysis

Tue, 07 Feb 2023 09:49:32 GMT

Whole Exome Sequencing (WES) Bioinformatic Analysis

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Whole Genome Sequencing (WGS) Bioinformatics Analysis

Tue, 07 Feb 2023 09:49:06 GMT

Whole Genome Sequencing (WGS) Bioinformatics Analysis

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Bioinformatics Analysis Service

Tue, 07 Feb 2023 09:48:35 GMT

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SuPrecision platform applications

Tue, 07 Feb 2023 09:48:02 GMT

NGS in genomic medicine has been driven by low cost, high throughput sequencing and rapid advances in our understanding of the genetic bases of human diseases. The NGS-based method has dominated sequencing space in genomic research, and quickly entered clinical practice. For the reason that unique features of NGS perfectly meet the clinical reality, the NGS technology is becoming a driving force to realize the dream of precision medicine. Moreover, lots of new computational and database-driven tools are emerging to aid in the interpretation of cancer genomic data as its use becomes more and more common in clinical evidence-based cancer medicine.

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NGS applications

Tue, 07 Feb 2023 09:47:33 GMT

Next-generation sequencing (NGS) technologies have progressive advantages in terms of cost-effectiveness, unprecedented sequencing speed, high resolution and accuracy in genomic analyses, thus are playing an increasing important role in fields of oncology and immunology.

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next-generation sequencing in oncology

Tue, 07 Feb 2023 09:47:04 GMT

next-generation sequencing in oncology

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next-generation sequencing for tumour detection

Tue, 07 Feb 2023 09:46:49 GMT

next-generation sequencing for tumour detection

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NGS for tumour detection

Tue, 07 Feb 2023 09:46:27 GMT

NGS for tumour detection

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Next-generation sequencing for cancer detection

Tue, 07 Feb 2023 09:46:01 GMT

Next-generation sequencing for cancer detection

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NGS for cancer detection

Tue, 07 Feb 2023 09:45:42 GMT

NGS for cancer detection

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Brain Tumor Vaccines

Fri, 30 Dec 2022 09:08:54 GMT

Malignant brain tumors are classified into primary and secondary (metastatic) brain tumors. Despite recent advancements in conventional therapies, such as surgery, radiation therapy, and chemotherapy, the prognoses for these tumors remain dismal. A variety of immunotherapy clinical trials are being conducted for both primary and secondary malignant brain tumors, including vaccine, checkpoint blockade, adoptive cell transfer, and oncolytic virus approaches.

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Head and Neck Cancers

Fri, 30 Dec 2022 09:08:30 GMT

Over the last decade, it has become clear that human papillomavirus (HPV) not only causes genital and anal cancers but also causes a subset of head and neck squamous cell carcinoma (HNSCC). In addition to the estimated ~492,800 cervical cancers caused worldwide by HPV each year, HPV also causes an estimated ~30,000 oropharyngeal cancers, HPV is detected in ~25% of all HNSCC, and the majority of these HPV-associated HNSCC are oropharyngeal (tonsillar and base of tongue) squamous cell cancers. As more and more information about the role of infection in non-cervical diseases is amassed, additional questions about whether prophylactic human papillomavirus vaccines will effectively prevent these conditions are raised. In fact, HPV is now the major cause of oropharyngeal cancer in developed countries, detected in 45–90% of cases. HPV has also been detected in a smaller subset of laryngeal and oral cavity cancers.

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Lung Cancer Vaccines

Fri, 30 Dec 2022 09:08:11 GMT

Lung cancer is by far the deadliest type of cancer in the United States and worldwide. The two major forms of lung cancer are non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC comprises about 85% of all lung cancers, and nearly all the cases are one of three major histologies: adenocarcinoma, squamous-cell carcinoma, and large-cell carcinoma. However, for most recent clinical trials, NSCLC has been divided into squamous and nonsquamous NSCLC. A great majority of nonsquamous disease is adenocarcinoma. Adenocarcinoma and squamouscell carcinoma have a similar etiology (generally cigarette smoking) and similar mutational load. However, there is a subset of NSCLC, usually adenocarcinoma, that is generally found in nonsmokers and is associated with specific genomic abnormalities, such as mutations in epidermal growth factor (EGF) receptor (EGFR) or rearrangements involving the anaplastic lymphoma kinase (ALK). Tumors from these patients generally have fewer mutations and are often clinically treated quite differently. SCLC comprises approximately 15% of the patients with lung cancer and it is almost always related to smoking. However, mutational load in SCLC is relatively low as compared to NSCLC. Although important new findings in the treatment of advanced NSCLC have led to significant progress, improvements have been incremental.

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Breast Cancer

Fri, 30 Dec 2022 09:07:53 GMT

Breast cancer is the most common malignancy diagnosed in women worldwide, with an estimated 1.7 million new cases in 2012. It remains a major public health problem even in developed countries, with more than 40,000 deaths in the United States annually. Optimization of standard therapies for breast cancer, including surgery, radiation therapy, endocrine therapy, and chemotherapy, has generated small but steady improvements in overall survival (OS) in the last 40 years. In the last 15 years, targeted therapies that inhibit critical pathways driving breast tumor growth and progression (such as the human epidermal growth factor receptor [HER-2], mammalian target of rapamycin [mTOR], and the cyclin-dependent kinases [CDKs]) have led to further improvements in clinical outcomes. Most recently, activating the immune system to reject breast cancers has emerged as a promising strategy for breast cancer therapy. Monoclonal antibodies that target the programmed death l (PD-1) pathway have demonstrated objective clinical responses in a subset of patients with triple negative breast cancer (TNBC) and luminal (estrogen receptor positive [ER+]) disease. This, together with the durable responses obtained with blockade of the PD-1 pathway across multiple solid tumor types, has sparked intense interest in developing effective immunotherapies for all breast cancer patients.

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Gastrointestinal Cancers

Fri, 30 Dec 2022 09:07:16 GMT

Gastrointestinal cancer refers to the malignant conditions of the gastrointestinal tract and digestive glands, including the esophagus, stomach, biliary tract, pancreas, small intestine, large intestine, rectum, and anus. Symptoms involving the affected organ may include abnormal bleeding, obstruction (resulting in difficulty swallowing or defecation), or other related problems. Diagnosis usually requires endoscopy, followed by biopsy of suspicious tissue. Treatment depends on the location of the tumor, the type of cancer cells, and whether it has intruded into other part of the body. These factors also determine the prognosis. In general, the gastrointestinal tract and accessory organs of the digestive (liver, pancreas, gallbladder) are responsible for more cancers and more likely to die of cancer than any other system of the body.

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Gynecologic Malignancies

Fri, 30 Dec 2022 09:06:56 GMT

For the most part, gynecological cancers can be treated for cure. As with the majority of solid tumor cancers, if gynecologic cancers are discovered at an early stage, surgery can be curative, and other treatments, such as radiotherapy or chemotherapy may be given post-operatively to consolidate treatment. All modalities of treatment can be considered in order to palliate symptoms and control disease growth, even if cure is not possible. As such, a multidisciplinary approach to the treatment of gynecologic cancers is necessary.

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Genitourinary Malignancies

Fri, 30 Dec 2022 09:06:38 GMT

Genitourinary cancers are cancers that affect the reproductive organs and the urinary system. The genitourinary tract traditionally includes the kidneys, the bladder, the tubes that collect and drain urine from the kidneys and drain it into the bladder (the ureters), the tube that drains urine from the bladder to the outside (the urethra), and specifically in men, the testicles and the prostate. The prostate is an accessory sex gland necessary for reproduction. Cancers that develop on the penis or in the adrenal glands are also classified as genitourinary cancers.

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Melanoma Vaccines

Fri, 30 Dec 2022 09:06:20 GMT

Melanoma, also known as malignant melanoma, is a cancer which develops from melanocytes (pigment-containing cells). Melanoma is the most dangerous type of skin cancer. Melanoma usually occurs in the skin, but rarely occurs in the intestines, mouth or eyes. Melanoma is more common in men than women. The main cause of melanoma is exposure to ultraviolet (UV) light in those people with low skin pigmentation. About 25% develop from moles with concerning changes including color changes, irregular edges, increased size, itchiness, or chapped skin. Those with more moles, family history, immunocompromised patients are more at risk.

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Cutaneous Tumors

Mon, 28 Nov 2022 09:01:27 GMT

Development services for different types of cutaneous tumors including melanoma, basal-cell skin carcinoma (BCC), squamous-cell skin cancer (SCC) and Merkel cell carcinoma (MCC), according to detailed requirements of customers.

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NGS Sequencing

Mon, 28 Nov 2022 09:01:07 GMT

Specialized in biomarker discovery and data analysis services, including NGS Sequencing.

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Chimeric VLP Based Vaccines

Mon, 28 Nov 2022 09:00:46 GMT

Chimeric VLP based vaccines design services according to customers' need.

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Biomarker Discovery & Development

Mon, 28 Nov 2022 09:00:23 GMT

Biomarker discovery and development services to evaluate vaccine efficacy, immunogenicity, safety, adjuvant benefits and manufacturing consistency.

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GLP Toxicology & Safety Testing

Mon, 28 Nov 2022 09:00:06 GMT

A series of GLP toxicology and safety testing to provide safety evidence for vaccine clinical trials and registration.

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GLP In Vivo ADME & PK Studies

Mon, 28 Nov 2022 08:59:46 GMT

A series of GLP in vivo ADME and PK Studies for vaccine development.

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GLP Reproductive Toxicology Studies

Mon, 28 Nov 2022 08:59:27 GMT

A series of GLP reproductive toxicology studies for vaccine development according to internationally recognized guidelines.

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Conjugation Method Design

Mon, 28 Nov 2022 08:58:42 GMT

Conjugation method design for hapten conjugate vaccines

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Conjugation Method Design

Thu, 10 Nov 2022 07:37:05 GMT

Conjugation method design for hapten conjugate vaccines

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Carrier Protein Design

Thu, 10 Nov 2022 07:36:03 GMT

Professional design services and a series of carrier proteins with the best quality and most competitive price.

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Controlled Release Vaccines Development

Thu, 10 Nov 2022 07:33:57 GMT

High-quality and cost-effective service with a focus on the development of controlled release technology of vaccines.

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Nanoparticles

Thu, 10 Nov 2022 07:33:27 GMT

A series of nanoparticles development for vaccine delivery with the best quality and most competitive price.

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Liposomes

Thu, 10 Nov 2022 07:32:31 GMT

A series of liposome development for vaccine delivery with the best quality and most competitive price.

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Carbohydrate Conjugate Vaccine

Thu, 10 Nov 2022 07:32:03 GMT

Personalized design and development strategies for carbohydrate conjugate vaccine.

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GMP Vaccine Production

Thu, 10 Nov 2022 07:31:43 GMT

GMP manufacturing of a variety of vaccines.

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Scale-up Development

Thu, 10 Nov 2022 07:31:10 GMT

Scale-up development to ensure a long-term supply of high-quality vaccines and mass production of the vaccine for worldwide use.

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Small-Scale Process Development

Sun, 23 Oct 2022 09:07:24 GMT

Creative Biolabs provides small-model generation to predict performance at scale and small-scale process development with scalability and repeatability.

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Evaluation of Expression System

Sun, 23 Oct 2022 09:06:41 GMT

Creative Biolabs provides comprehensive information about protein expression for vaccine development and will help you choose the right expression system for your specific applications.

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Micelles

Sun, 23 Oct 2022 09:05:56 GMT

Creative Biolabs offers our clients a series of Micelle-based adjuvants for vaccine delivery with the best quality and most competitive price.

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Adjuvant Optimization

Sun, 23 Oct 2022 09:05:12 GMT

Creative Biolabs’ adjuvant optimization strategies can provide you with the best advice and accelerate your vaccine development program.

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Delivery System Optimization

Sun, 23 Oct 2022 09:04:39 GMT

Creative Biolabs’ Delivery System Optimization strategies can provide you with the best advice and accelerate your vaccine development program.

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Formulation Optimization

Sun, 23 Oct 2022 09:03:57 GMT

Creative Biolabs’ formulation optimization strategies can provide you with the best advice and accelerate your vaccine development program.

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Vaccine Assessment In Vivo Assays

Sun, 23 Oct 2022 09:03:20 GMT

Creative Biolabs offers our customers a series of in vivo assays to enlighten the long and grueling path of vaccine development.

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Vaccine Assessment In Vitro Assays

Sun, 23 Oct 2022 09:02:31 GMT

Creative Biolabs offers a series of preclinical in vitro assays to ensure and enlighten the long and grueling path of vaccine development.

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Subunit Vaccine Design

Tue, 27 Sep 2022 14:19:55 GMT

Vaccine design services such as subunit vaccine design.

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Live Attenuated and Killed Vaccine Design

Tue, 27 Sep 2022 14:19:32 GMT

vaccine design service including live attenuated and killed vaccines.

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In silico Vaccine Design

Tue, 27 Sep 2022 14:19:00 GMT

In silico service for vaccine, which provides a way to predict and design new vaccine and vaccine components.

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Process Development & GMP Manufacturing

Tue, 27 Sep 2022 14:18:37 GMT

Process Development and GMP Manufacturing services to support your vaccine development and commercialization efforts.

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Formulation Development

Tue, 27 Sep 2022 14:18:15 GMT

Vaccine formulation related services including Formulation Optimization, Adjuvant Selection and Delivery System Selection

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Vaccine Analytical Development & Qualification

Tue, 27 Sep 2022 14:17:51 GMT

Vaccine Analytical testing programs for live attenuated vaccine, inactivated vaccine, subunit vaccine, vector vaccine, conjugate vaccine, DNA and RNA vaccine.

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Adjuvant Selection

Tue, 27 Sep 2022 14:17:33 GMT

vaccine adjuvants synthesis and PRR Ligands scanning services

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Vaccine Technology

Tue, 27 Sep 2022 14:17:13 GMT

All kinds of Vaccine Technology that include Vaccine Target Validation, Monoclonal Antibody Vaccines, Cell Based Vaccines and more

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Coronavirus

Wed, 24 Aug 2022 02:33:17 GMT

Coronaviruses are species of virus belonging to the family Coronaviridae. Coronaviruses are enveloped viruses with a positive-sense single-stranded RNA genome and with a nucleocapsid of helical symmetry. The genomic size of coronaviruses ranges from approximately 26 to 32 kilobases, the largest for an RNA virus. Coronaviruses primarily infect the upper respiratory and gastrointestinal tract of mammals and birds. Six different currently known strains of coronaviruses infect humans. The much-publicized human coronavirus, SARS-CoV which causes SARS, has a unique pathogenesis because it causes both upper and lower respiratory tract infections.

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Chikungunya Virus

Wed, 24 Aug 2022 02:32:58 GMT

The chikungunya virus (CHIKV) is the major cause of Chikungunya. Chikungunya virus is a member of the alphavirus genus and Togaviridae family. The virus is spread between people by two types of mosquitos: Aedes albopictus and Aedes aegypti. The virus may circulate within a number of animals including birds and rodents. The virus is spread between people by two types of mosquitos: Aedes albopictus and Aedes aegypti. The virus may circulate within a number of animals including birds and rodents. Symptoms include fever and joint pain. Other symptoms may include headache, muscle pain, joint swelling, and a rash. The symptoms can be mistaken for those of dengue fever and Zika fever. The risk of death is around 1 in 1,000. The very young, old, and those with other health problems are at risk of more severe disease.

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Canine Distemper Virus

Wed, 24 Aug 2022 02:32:41 GMT

Canine distemper virus (CDV) is a single-stranded RNA virus of the family paramyxovirus, and thus a close relative of measles and rinderpest. The disease is highly contagious via inhalation. It is most commonly associated with domestic animals such as dogs and ferrets, although it can infect wild animals as well. Despite extensive vaccination in many regions, it remains a major disease of dogs.

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Bluetongue Virus

Wed, 24 Aug 2022 02:32:01 GMT

Bluetongue (BT) virus is a member of genus Orbivirus, Reoviridae family. Twenty-six serotypes are now recognised for this virus. Unlike other arboviruses, BTV lacks a lipid envelope. BTV causes an acute disease with high morbidity and mortality in sheeps, goats, cattle and other domestic animals as well as wild ruminants. Major signs are swelling of the face and tongue, excessive salivation, high fever, and cyanosis of the tongue.

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Astrovirus

Wed, 24 Aug 2022 02:31:41 GMT

Astrovirus is a type of virus that was first discovered in 1975 using electron microscopes following an outbreak of diarrhoea in humans. In addition to humans, astroviruses have now been isolated from numerous mammalian animal species and from avian species such as ducks, chickens, and turkey poults. Astroviruses are 28-35 nm diameter, icosahedral viruses that have a characteristic five- or sixpointed star-like surface structure when viewed by electron microscopy. Human astroviruses have been shown in numerous studies to be an important cause of gastroenteritis in young children worldwide.

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Aquareovirus

Wed, 24 Aug 2022 02:31:22 GMT

Aquareovirus (AQRV) is a genus of the Reoviridae family, which currently contains a total of seven species, of which Aquareovirus A is a typical species. The host of the virus of this genus is fish, crustacean and shellfish. Usually, Aquareoviruses are weak or not pathogenic to fish, but sometimes cause hemorrhagic diseases, pancreatitis and hepatitis. The virions contain no envelope, are icosahedral in shape, have a diameter of about 75 nm, and the virus encodes a total of 12 proteins.

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Adenovirus

Wed, 24 Aug 2022 02:31:06 GMT

Adenoviruses (members of the family Adenoviridae) are medium-sized (90-100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double stranded DNA genome. They have a broad range of vertebrate hosts; in humans, more than 50 distinct adenoviral serotypes have been found to cause a wide range of illnesses, from mild respiratory infections in young children (known as the common cold) to life-threatening multi-organ disease in people with a weakened immune system.

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Antigen Products for Vaccine Development

Wed, 24 Aug 2022 02:30:40 GMT

In immunology, an antigen is a molecule capable of inducing an immune response (to produce an antibody) in the host organism.

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Ag-Fc Fusion Protein Vaccine for Cancer

Mon, 25 Jul 2022 09:46:17 GMT

Conquering cancer has been the focus of attention of surgeons and scientists for a long time. To this end, the scientific community has carried out a lot of exploration and put forward many theories and effective strategies.

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Cancer Immunotherapy by Antisense Suppression of Ii Protein

Mon, 25 Jul 2022 09:46:00 GMT

Ii protein suppression, as a promising antisense drug therapy, significantly enhances the immunogenicity of antigenic epitopes presented by tumor cell major histocompatibility complex class II.

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li Suppression Technology for DNA Vaccine

Mon, 25 Jul 2022 09:45:33 GMT

The core of this platform is to produce an effective vaccine by inhibiting Ii with Ii antisense oligonucleotides, which also effectively inhibits Ii expression in dendritic cells (DC), resulting in the presentation of endogenously expressed ovalbumin (OVA) epitopes to CD4+ T cells and a potent tumor vaccine.

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MHC Class II-associated li Protein Suppression Technology

Mon, 25 Jul 2022 09:45:09 GMT

The cell surface form of the invariant chain (li) is called CD74, which is a type II protein consisting of a short cytoplasmic tail, a transmembrane region, and a luminal domain.

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Antibody-antigen-adjuvant Conjugates

Mon, 25 Jul 2022 09:44:38 GMT

Antibody-antigen conjugates promote antigen presentation by targeted delivery of antigens to specific regions, representing a powerful vaccination approach.

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Antibody-cytokines Conjugates

Mon, 25 Jul 2022 09:44:17 GMT

Cytokines, which modulate the balance between cell-based and humoral immune responses, are important in cell signaling and immune system.

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Antibody-toxins Conjugates

Mon, 25 Jul 2022 09:43:57 GMT

An effective cancer vaccine must be capable of generating potent anti-tumor immune responses and overcoming the mechanisms of tolerance mediated by the progressive tumor itself.

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How Does a Microfluidic Cell-squeezing Device Work?

Mon, 25 Jul 2022 09:43:13 GMT

Cell-disrupting pressure change is achieved by passing the cells through a narrow opening in the microfluidic device which consists of a channel etched into the wafer.

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Antibody-antigen Fusion Technology for Cancer Vaccine

Fri, 24 Jun 2022 09:33:10 GMT

An effective cancer vaccine must be capable of generating potent anti-tumor immune responses and overcoming the mechanisms of tolerance mediated by the progressive tumor itself.

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Microfluidic Cell-squeezing Technology for B Cell-based Vaccine

Fri, 24 Jun 2022 09:32:01 GMT

Rapid mechanical deformation of cells has become a promising, vector-free method for intracellular delivery of nanomaterials and macromolecules, which opens new possibilities for cellular vaccine.

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Biomarker Discovery for Cancer Vaccine

Fri, 24 Jun 2022 09:31:03 GMT

The low success rate of immunotherapy for cancer requires us to understand the immune mechanism in depth, and the determination of biomarkers that can predict the therapeutic effect may be a means to enhance the success of cancer vaccines.

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Vaccine Combination Immunotherapy

Fri, 24 Jun 2022 09:30:31 GMT

Immunotherapy has become a rising star in the treatment of cancer, but not all patients have a good response to checkpoint blockade, so the combination with other therapies becomes a practical necessity.

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Anti-Tregs Immune-modulating Anti-cancer Technology

Fri, 24 Jun 2022 09:30:02 GMT

The immune system consists of many types of regulatory cells [e.g., regulatory T cells (Tregs), M2 macrophages, myeloid-derived suppressor cells (MDSCs), and different dendritic cell subtypes], which control the strength of the immune response.

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Cytokine Development to Enhance Antigen Presentation

Fri, 24 Jun 2022 09:29:05 GMT

Cytokines have been used to treat advanced cancers, including renal cell carcinoma and metastatic melanoma with some success, but systemic administration is associated with marked toxicity.

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Immune Monitoring Assays of Cancer Vaccines

Fri, 24 Jun 2022 09:26:57 GMT

The discipline of immune monitoring for cancer vaccine and immunotherapy trials is experiencing an era of unparalleled growth because of an increased understanding of the fundamental basis of human cancer and host–tumor interactions.

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Tumor-APC Fusion Technology

Fri, 24 Jun 2022 09:26:08 GMT

A novel development in cancer vaccines is the use of tumor-APC fusion technology. Fusions of tumor cells and antigen presenting cells have been investigated in animal models and clinical trials as candidate cancer vaccines.

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Ty21 Based Vaccines for Cancer

Sun, 15 May 2022 06:05:44 GMT

The Ty21 vaccine has been inoculated to millions of people as a live attenuated bacterial vaccine and has been proven to be safe and well tolerated.

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Cytomegalovirus-based Cancer Immunotherapy

Sun, 15 May 2022 06:02:38 GMT

The emergence of various immunotherapies has brought hope and dawn to the treatment of cancer. Among the many immunotherapies, cytomegalovirus has become a blockbuster for cancer treatment because of its unique advantages.

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BCG Vaccines for Cancer

Sun, 15 May 2022 06:01:09 GMT

Taking advantage of animal and immunologic studies that defined optimal conditions for BCG response, urologists have developed BCG into the most effective treatment currently available in the treatment of aggressive superficial bladder cancer. A number of cancer vaccines use BCG as an additive to provide an initial stimulation of the person's immune systems.

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Fully Synthetic Carbohydrate Based Cancer Vaccines

Sun, 15 May 2022 06:00:24 GMT

Although exposure to tumor-associated oligosaccharides alone is not sufficient to evoke an immune response, when tumor associated carbohydrate antigens are presented to the immune system as glycoconjugates, appended to the appropriate immunogenic carrier molecules, antibody formation may be observed.

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Vector Based Vaccines

Sun, 15 May 2022 05:59:19 GMT

The advantages of vector-based vaccines include 1) Multiple delivery of TAAs at one time; 2) Vector itself is immunogenic, boosting the overall immune response; 3) Speedy and easy production. Besides virus vector, unharmful bacteria, yeast cells or other structures can also be used as vector to deliver the TAAs into the body.

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mRNA Cancer Vaccines

Sun, 15 May 2022 05:55:44 GMT

During the last decade, mRNA became increasingly recognized as a versatile tool for the development of new innovative therapeutics. Especially for vaccine development, mRNA is of outstanding interest and numerous clinical trials have been initiated.

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DNA Based Cancer Vaccines

Sun, 15 May 2022 05:55:02 GMT

Nucleic acid immunization has garnered much attention as a promising approach for cancer therapeutic development. This innovative vaccine strategy uses non-live, non-replicating, non-spreading DNA formulations which utilize the host’s cellular machinery for expression of proteins (antigens).

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Anti-Idiotype Vaccines

Sun, 15 May 2022 05:51:15 GMT

The use of anti-idiotype (Id) antibodies as vaccines to stimulate antitumor immunity is one of several promising immunologic approaches to the therapy of cancer.

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Dendritic Cell Vaccines

Sun, 15 May 2022 05:50:28 GMT

Dendritic cells (DCs) break the antigens on the cancer cell surfaces into smaller pieces. The dendritic cells then act as most-wanted posters for the immune system, displaying those antigen pieces to the killer T cells.

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Tumor Cell Vaccines

Sun, 15 May 2022 05:41:51 GMT

Autologous and allogeneic tumor cells were one of the first types of tumor vaccines to be used.

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Personalized Neoantigen Cancer Vaccine

Sun, 15 May 2022 05:41:04 GMT

Non-mutated tumor-associated antigens and mutant antigens that present only in tumor cells are general targets for cancer vaccines. The latter are also called neoantigens and because of their presence only in cancer cells, there are no central tolerance and autoimmunity concerns.

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Advantages of mRNA as Therapeutics

Sun, 10 Apr 2022 03:25:50 GMT

Although mRNA-based gene therapy is not as well studied as DNA-based gene therapy, the use of mRNA as therapeutics holds many critical advantages. Compared with conventional therapeutic strategies and DNA-based gene therapy, the potential virtues of mRNA-based gene treatment mainly include:

mRNA therapy is effective in both mitotic and non-mitotic cells since mRNA is delivered directly into the cytoplasm rather than integration into the nucleus of DNA-based gene therapy;

Significantly reduced risk of insertional mutagenesis and enhanced safety without intervening in the human genome;

Permit a rapid and transient expression of the desired protein;

Allow for translation natural and fully functional proteins under the cell's machinery and physiological conditions;

The immunogenicity of the therapeutic mRNA can be modified by chemical modifications according to the applications, such as slightly increased immunogenicity to improve the performance of the mRNA vaccine.

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mRNA-Based Gene Therapy

Sun, 10 Apr 2022 03:25:22 GMT

Gene therapy is an experimental technique using nucleic acids as a therapeutic drug to treat disease, which has held great potential to be a preferred treatment option for many diseases. According to the types of therapeutic nucleic acids, gene therapy is generally divided into DNA-based gene therapy and RNA-based gene therapy. Unlike DNA-based gene therapy that introduces a specific DNA fragment into the genome, RNA-based gene therapy delivers a therapeutic RNA into the cytoplasm of target cells, among which messenger RNA (mRNA)-based therapy has emerged as an attractive method in a wide range of therapeutic applications.

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mRNA Application in Research

Sun, 10 Apr 2022 03:22:35 GMT

In recent years, a number of mRNA-based technologies, such as mRNA display technology, LPR technology, have been generated for discovering new peptides or protein ligands for mRNA, analyzing the interaction between drugs and target proteins, as well as boosting immune responses against viral infections and cancers. Moreover, many kinds of mRNA-based vaccine technologies have also been exclusively studied for casting light on the mRNA construct, mRNA formulation, and mRNA adjuvanticity, mRNA immunological characteristics.

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Applications of mRNA as Research Tools

Sun, 10 Apr 2022 03:22:03 GMT

Messenger ribonucleic acid (mRNA), a type of RNA molecule that can be found in various cells. In general, the structure of mRNA is often composed of a 5' cap, two untranslated regions (5' UTR and 3' UTR), a coding domain, a 3' poly(A) tail. mRNA can be produced during the process of transcription in the nucleus. Normally, primary transcript mRNA (pre-mRNA) will be created at the early stage of transcription. This pre-mRNA will be further processed into mature mRNA by RNA splicing and removing introns. Mature mRNA can be further transported into the cytoplasm to participate in protein synthesis. Moreover, two main types of RNA molecules, transfer RNA (tRNA) and ribosomal RNA (rRNA), have also been identified that play a critical role in translating codons into amino acids in the protein-manufacturing process.

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Construction and Applications of Gemini Surfactants

Sun, 10 Apr 2022 03:21:21 GMT

Drug carriers based on liposomes or drug/lipid complexes present great potential in multiple applications, including drug targeting, target delivery, gene therapy, and antibacterial treatments. In preclinical and clinical trials, a variety of synthetic lipids and surfactants have been designed and constructed to further improve the performances of liposomes and drug/lipid complexes, such as higher transfection efficiency, lower toxicity, strong target selectivity, as well as efficient cell membrane fusion and cell uptake.

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Classification of Surfactants

Sun, 10 Apr 2022 03:20:37 GMT

Ionic Surfactants

Non-Ionic Surfactants

Amphoteric Surfactants

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Introduction to Surfactants

Sun, 10 Apr 2022 03:20:07 GMT

Surfactant, also known as the surface-active agent, is a general term for compounds that can reduce the surface tension between two liquids, between gas and liquid, or between liquid and solid. The molecular structure must contain both hydrophilic (water-soluble) and lipophilic (soluble in lipid or oil) parts. Now surfactants have been widely used in the construction of lipid nanoparticles (LNPs) for drug delivery.

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In vitro Transcription Vector

Sun, 10 Apr 2022 03:19:30 GMT

Transcription of RNA is started with the appropriate choice of IVT vector that contains promoter sequence (T3, T7 or SP6) for generating high yields of transcript, appropriate restriction sites for cloning of the gene of interest (GOI), 5' UTR, 3' UTR, and/or a polyA tail. Typically, T7 is a standard and well-described polymerase used to transcribe a linearized DNA template into RNA. Therefore, it is often necessary to optimize the structural elements in the IVT vectors for stable expression of target proteins.

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In vitro Transcription Introduction

Sun, 10 Apr 2022 03:18:55 GMT

IVT has received increasing attention as a powerful alternative genetic material by exogenous delivery for protein expression. Compared with conventional pDNA expression, IVT mRNA-based protein expression has several advantages: 1) mRNA can directly encode the protein through a single translation step; 2) mRNA has extremely high protein expression comparable to viral systems; 3) rapid onset time for the expression of target proteins; 4) mRNA is a non-viral system that relieves some safety concerns; 5) plasmid-based template by IVT meets the synthetic demands for long RNA (up to thousands of bases).

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ARCA-capped mRNA Synthesis Kit

Sun, 10 Apr 2022 03:17:55 GMT

Anti-reverse cap analog (ARCA)-capped mRNA synthesis kit includes all the critical reagents for in vitro transcription to generate high yields of high-quality mRNA efficiently.

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mRNA Purification Kit

Sun, 10 Apr 2022 03:17:27 GMT

mRNA purification kits are designed to isolate intact messenger RNA from cells, tissues, or RNA preparations for downstream applications in the study of gene expression and transcriptome. The mRNA purification kit allows yield pure, high-quality mRNA.

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mRNA Kits

Sun, 10 Apr 2022 03:16:41 GMT

mRNA Isolation Kit

The mRNA isolation kit contains all necessary reagents and enough buffers for the isolation of mRNA from total RNA samples in less than one hour. mRNA isolation kits optimize the isolation of mRNA from different sample sizes or total RNA. The mRNA isolation kit allows for efficient and reproducible isolation of high-purity mRNA and permits the manual processing of multiple samples. It prepares large yields of highly purified mRNA from mammalian cells, tissue, and total RNA. The highly purified mRNA may be used directly in many molecular biology applications, such as RT-PCR, cDNA synthesis, northern blotting, northern ELISA, RNase protection assay, and even in vitro translation.

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RNA Methylation Assay

Sun, 06 Mar 2022 07:42:12 GMT

RNA methylation is a reversible post-translational modification to RNA that plays a significant role as an epigenetic mechanism and epigenetically impacts numerous biological processes.

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RNA Fluorescence Assay

Sun, 06 Mar 2022 07:38:56 GMT

Nucleic acid detection and quantitation are essential to the performance of many molecular biology protocols. Accurate RNA quantitation is a critical step in obtaining successful results using complex molecular biology techniques, such as reverse transcription PCR and differential display PCR. The fluorescent-based RNA assay should be useful in determining yields of purified cellular RNAs and in vitro transcribed RNA and for subsequent manipulations and analyses, such as Northern blotting, RNase protection assays, cDNA library preparation, and reverse transcription PCR.

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PrimeFlow RNA Assay

Sun, 06 Mar 2022 07:36:25 GMT

PrimeFlow RNA Assay is based on the flow cytometry assay and in situ hybridization which combines the power of the single-cell resolution with branched-DNA signal amplification technology.

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Nuclease Protection Assay

Sun, 06 Mar 2022 07:34:35 GMT

Nuclease protection assay is extremely sensitive for the detection, quantitation, and mapping of specific RNAs in complex mixtures of total cellular RNA.

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mRNA-based Assays

Sun, 06 Mar 2022 07:29:51 GMT

According to the different goals and expected applications, different assays may need to be designed and prepared.

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mRNA Interactome Capture

Sun, 06 Mar 2022 07:28:55 GMT

mRNA interactome capture (RIC) is a recently developed method for extensive and unbiased identification of active RBPs in living cells, which allows systematically capturing all RNA-protein interactions that occur in the transcriptome at a specific time.

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RAP for RNA-Protein Interactions Analysis

Sun, 06 Mar 2022 07:28:08 GMT

RNA antisense purification (RAP) is a novel technology for the detection of RNA-RNA and RNA-protein interactions. Developed by Engreitz et al. in 2013, RAP was an RNA-centric biochemical purification method mainly designed for the characterization of large noncoding RNA (lncRNA)-a group of critical regulators in chromatin structure, gene expression, and cellular activities.

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ChIRP for RNA-Protein Interactions Analysis

Sun, 06 Mar 2022 07:24:51 GMT

ChIRP-seq is one powerful in vivo high-throughput technology, which can enrich the discovery of RBPs and DNA.

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CLIP-seq for RNA-Protein Interactions Analysis

Sun, 06 Mar 2022 07:22:30 GMT

The high-throughput sequencing of RNA fragments isolated by crosslinking immunoprecipitation (CLIP-seq) is one of the standard techniques for the identification of wide binding sites in the transcriptome of target RNA binding proteins.

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RIP-seq for RNA-Protein Interactions Analysis

Sun, 06 Mar 2022 07:21:00 GMT

RNA binding protein (RBP) plays an important role in the coordination of different levels of gene expression control and post-transcriptional regulation.

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RNA-Protein Interactions Analysis

Sun, 06 Mar 2022 07:18:04 GMT

RNA and proteins are interconnected biomolecules that can influence the fate of each other and function through physical interactions. Therefore, the importance of RNA-protein interactions in controlling many aspects of gene regulation is increasingly appreciated. Technologies to examine RNA-protein interaction have been developed from DNA-protein interaction technologies.

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In Silico mRNA Structure Prediction

Sun, 06 Mar 2022 07:16:50 GMT

In silico prediction and modeling is an important tool used to obtain RNA secondary structure. This method is either a sequence-based prediction or 3D structure-based assessment routines.

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mRNA Vaccines Development

Wed, 09 Feb 2022 13:58:57 GMT

Cancer neoantigens derived from random somatic mutations in tumor tissue represent an attractive type of target for the cancer vaccine. Vaccination against the tumor-specific neoantigens minimizes the potential induction of central and peripheral tolerance as well as the risk of autoimmunity.The most straightforward use of mRNA vaccines in oncologic settings is the immunization of patients with mRNA vaccines encoding tumor-associated antigens (TAAs).

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mRNA Pharmacology Optimization

Wed, 09 Feb 2022 13:57:37 GMT

In vitro transcribed (IVT) messenger RNA (mRNA) has recently come into focus as a potential new drug class to deliver genetic information. Such synthetic mRNA can be engineered to transiently express proteins by structurally resembling natural mRNA.

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Therapeutic Antibody-coding mRNA

Wed, 09 Feb 2022 13:56:20 GMT

An elegant solution to circumvent the problems of complex production, purification processes and aberrant post-translational modifications of the monoclonal antibody (mAb), is to deliver the genetic information of the antibody itself.

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mRNA for Regenerative Medicine

Wed, 09 Feb 2022 13:55:24 GMT

Regenerative medicine is a branch of modern medicine that seeks to develop novel methods for replacing, repairing, or healing damaged cells, tissues, and organs. Pilot studies have shown that regenerative medicine has been widely used for treating a wide array of disease conditions, such as progressive disorders, diabetes, as well as arthritis.

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Introduction to Protein Replacement Therapy

Wed, 09 Feb 2022 13:53:44 GMT

Proteins have been considered as key molecules in humans, and they have proven their significant roles in regulating physiological and biological reactions, protecting the human body from viral and bacterial infections. In the past few years of studies, a wide variety of human diseases have been associated with different proteins. Moreover, most natural and modified proteins have been generated by various advanced technologies, such as genetic engineering and protein engineering, to be further expressed by different systems, including phage display technology.

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Introduction of Gene Therapy

Wed, 09 Feb 2022 13:52:08 GMT

Gene therapy has shown promising results in the treatment of human diseases, including tumors, autoimmune disorders, and infectious diseases.

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mRNA for Immunotherapy

Wed, 09 Feb 2022 13:45:54 GMT

mRNA, a single-stranded RNA, is usually produced in the process of transcription that plays an important role in protein synthesis and disease therapy. In general, mRNA can be created in the nucleus and be further transported into the cytoplasm to make proteins bind to specific mRNAs. Transfer RNA (tRNA) and ribosomal RNA (rRNA) are the main types of RNA molecules that are essential for forming ribosomes and mRNA transcription.

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Introduction to mRNA Therapeutics

Wed, 09 Feb 2022 13:44:32 GMT

mRNA is usually created during the process of in vitro transcription (IVT) of various linearized pDNAs or PCR products. It is composed of a promoter domain (5' cap), 5' and 3' untranslated regions (UTRs), an open reading frame (ORF), as well as a poly(A) sequence.

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Assay Development

Wed, 09 Feb 2022 13:43:19 GMT

Modulation of mRNA stability provides a powerful tool for controlling gene expression during the physiological transitions and regulatory processes.

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Tet-off Regulatory Promoter System

Wed, 09 Feb 2022 13:41:16 GMT

The Tet-regulatory system has several advantages over other approaches used to measure mRNA half-life. The Tet-regulatory system provides the opportunity to study the regulation under physiologically relevant and undisturbed conditions and to investigate mechanisms underlying differential and selective mRNA turnover in mammalian cells.

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c-fos Serum-inducible Promoter System

Wed, 09 Feb 2022 13:38:49 GMT

Among the genes most studied concerning, mRNA stability is the protooncogenes involved in the early response to growth factors, especially c-fos. Transcription of c-fos is rapidly induced by growth factors and other extracellular stimuli and then ceases completely within minutes after its activation. This transient accumulation and tight control of c-fos mRNA appears to be critical to normal cellular function. Moreover, monitoring this rapid decay has permitted the direct measurement of c-fos mRNA turnover under conditions of serum stimulation. This approach provides a tight genetic switch to control transcription for studying mRNA turnover without the use of transcription inhibitors.

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Actinomycin D-based Method

Wed, 09 Feb 2022 13:36:29 GMT

Methods of mRNA stability tests such as transcription inhibition initially are proved most amenable for high-throughput technologies. Actinomycin D is a fast-acting DNA intercalator which is widely used as a transcription inhibitor to achieve mRNA inhibition in mRNA stability assays. The level of an mRNA transcript could be quantified to measure the half-life of specific mRNAs either when the mRNA is in a steady-state or after the inhibition of mRNA synthesis by actinomycin D.

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mRNA Stability Test

Wed, 05 Jan 2022 06:30:27 GMT

mRNA stability is the major control point in gene expression regulation. Changes in mRNA stability are intimately related to alterations in gene expression regulation. mRNA stability is highly regulated by the interactions between structural elements of an mRNA transcript and a plethora of specific RNA-binding proteins. The deregulated mRNA stability could result in the aberrant accumulation of mRNAs and the proteins they encode. Different cellular processes, such as cell cycle progression, cell differentiation, and embryonic development are modulated by changes in mRNA stability.

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Custom iPS Cell Reprogramming by mRNA

Wed, 05 Jan 2022 06:29:48 GMT

Non-integrative mRNA reprogramming has proven to be the most efficient and clinically-relevant method for human induced pluripotent stem cells (iPSCs) reprogramming.

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Custom B Cell Reprogramming by mRNA

Wed, 05 Jan 2022 06:26:45 GMT

B cell reprogramming refers to the ability to redefine the identity of B cell by changing its epigenetic and transcriptional landscapes, reflected in the acquisition of new morphological, molecular, and functional features.

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Custom Natural Killer Cell Reprogramming by mRNA

Wed, 05 Jan 2022 06:26:10 GMT

Natural killer (NK) cells are cytotoxic immune cells that play an important role in the defense against cancer. Genetic manipulation of NK cells to improve their persistence, tumor-targeting capacity, and the ability to home to disease sites in vivo may further enhance the efficacy of NK cell-based cancer immunotherapy.

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Custom Dendritic Cell Reprogramming by mRNA

Wed, 05 Jan 2022 06:25:29 GMT

Dendritic cells (DCs) play important roles in anti-tumor immune responses and reprogramming of the DCs by mRNA has shown clinical promise in recent years.

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Custom T Cell Reprogramming by mRNA

Wed, 05 Jan 2022 06:21:48 GMT

T cells play crucial roles in mounting effective immune responses that affect therapeutic interventions in cancer, infectious disease, and autoimmunity. It has been revealed that T cells can be programmed with molecular modules to increase their therapeutic potency and specificity, especially in adoptive cell therapy (ACT) for cancers. Genetically reprogrammed T cells hold great promise in the areas of ACT, offering great hope for curative responses in cancer patients.

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Custom mRNA-based Cell Reprogramming

Wed, 05 Jan 2022 06:20:59 GMT

mRNA reprogramming technology is the most unambiguously "footprint-free", most productive, and most suitable method for clinical production of induced pluripotent stem cells (iPSCs). It holds great promise in the areas of disease modeling and regenerative medicine and shows unique commercial potential.

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Cationic Nanoemulsion

Wed, 05 Jan 2022 06:20:16 GMT

Cationic nanoemulsion (CNE) is a very effective nonviral delivery system to successfully deliver therapeutic mRNA. Moreover, it can improve the transfection of nucleic acids and has been evaluated as one hybrid vector for delivering self-amplifying mRNA vaccines.

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Lipopolyplex

Wed, 05 Jan 2022 06:19:35 GMT

Lipopolyplex is a ternary complex of cationic liposome, polycation and nucleic acid. It is the second generation of non-viral gene vector developed after the first generation of cationic liposome complex. Specifically, mRNA molecules are encapsulated in a polymer core loaded into a phospholipid bilayer shell structure. The obtained structure can not only protect the mRNA molecules in the multi-node core structure from the attack of RNA enzyme, but also be internalized effectively by dendritic cells (DCs). In DCs, particles are transported through the vector system, and the mRNA molecules are released into the cytoplasm to generate antigens.

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Hybrid Vectors

Wed, 05 Jan 2022 06:18:30 GMT

The hybrid vectors usually integrate several potential advantages of their components. Specifically, they usually share a core-shell structure, and the properties of the 'core' can be adjusted to respond to external stimuli that facilitate the escape of the endosome; at the same time, the 'shell' can enhance the stability and pharmacokinetics of the nanoparticles and give the surface adjustable properties. IVT

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Introduction t Micelleplex

Wed, 05 Jan 2022 06:16:39 GMT

Micelleplexes have the same characteristics as polymeric micelles. They are composed of amphiphilic polymers (diblock, triblock or graft copolymers). In an aqueous environment, they can self-assemble into a micelle structure composed of a hydrophilic shell and hydrophobic core. Hydrophobic core forms the microenvironment of hydrophobic drug binding through hydrophobic interaction, while hydrophilic corona-forming components of polymer micelles often interfere with RNA binding. In turn, the hydrophilic corona is responsible for stabilizing micelles in the plasma and preventing phagocytosis/conditioning by minimizing non-specific interactions with biological components.

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Polyplex

Wed, 05 Jan 2022 06:15:46 GMT

Cationic polymer/therapeutic gene complexes (cationic polyplexes) can improve the cellular uptake of nucleic acid therapy drugs by interacting with negatively charged cell surface. The advantages of using cationic polyplexes include the protection of therapeutic genes from the influence of serum nucleases. The complexation of anionic mRNA molecules and cationic polymers occurs spontaneously through electrostatic interactions, forming polyplexes with multi-chains. They usually show higher stability than lipid complexes. It is also easy to modify polymers such as molecular weight, geometry (linear or branched) and ligand linkage.

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Polymer-based Vectors

Mon, 29 Nov 2021 08:46:55 GMT

Polymers, a class of natural or synthetic substances composed of very large molecules, are multiples of simpler chemical units. Polymeric nanoparticles (PNPs) are the most common materials studied as nanocarriers for drugs and gene delivery. Generally, polymers designed and studied for gene delivery include polyethyleneimine (PEI) and its derivatives; polymethacrylate; carbohydrate-based polymers, usually β-cyclodextrin, chitosan, dextran, and poly(glycosylamine) as their carbohydrate functional groups; dendrimer-based vectors, such as polyamidoamine dendrimers (PAMAM) and poly(propylene diamine) (PPI) dendrimers, etc.

The preparation of PNPs includes two methods: a top-down strategy (grinding prefabricated polymers to appropriately sized particles) or a bottom-up strategy (requiring the use of conventional multi-reaction direct polymerization monomers).

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Lipid Nanoparticle

Mon, 29 Nov 2021 08:45:09 GMT

LNPs are one of the most mature mRNA delivery materials. They are one of the new potential delivery systems in the 100-150 nm range and can be used as alternative materials for polymers. LNP formulations usually consist of (1) an ionizable or cationic lipid or polymer materials containing tertiary or quaternary amines to encapsulate polyanion mRNA; (2) an amphoteric lipid which is similar to the lipid membrane in cells; (3) cholesterol stabilized LNP lipid bilayer; and (4) a polyethylene glycol (PEG)-lipid, which makes nanoparticles have a hydrated layer, improves colloidal stability and reduces protein absorption.

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Lipoplex

Mon, 29 Nov 2021 08:43:26 GMT

mRNA is frequently encapsulated with positively charged liposomes to form lipoplexes. Lipoplexes are self-assembling nanosystems and their formation entails a multistep mechanism as revealed by detailed studies employing monolayers, atomic force microscopy and cryo-electron microscopy. In a millisecond first step, electrostatic interactions between phosphate and the positively charged amine headgroup of the cationic lipid occur. The cellular uptake is mainly mediated by either lipoplex endocytosis or endocytosis-like mechanisms. Moreover, lipoplex delivery systems have substantial advantages like easy synthesis, low batch variability, scalability, and biocompatibility. It has also been noted that drug delivery systems in the nano-range enhance the pharmacokinetic availability of encapsulated drugs.

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Lipid-based Vectors for mRNA Delivery

Mon, 29 Nov 2021 08:41:49 GMT

Lipid-based Vectors for mRNA Delivery

Lipoplex (LP)
Lipid nanoparticle (LNP)
Cationic nanoemulsion (CNE)
Lipid-like delivery molecules
Nanostructured lipid carriers (NLCs)

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mRNA Delivery Vehicle

Mon, 29 Nov 2021 08:40:59 GMT

mRNA has several advantages over DNA for gene transfer and expression, including the lack of any requirement for nuclear localization or transcription and the nearly negligible possibility of genomic integration of the delivered sequence. After over two decades of development, mRNA has broad potential as a therapeutic. The design and chemistries used to synthesize mRNAs have advanced to a point where they enable adequate stability and immune evasion, while at the same time allowing the maintenance of efficacy and specificity. Current clinical efforts are focused on vaccination, protein replacement therapies, and treatment of genetic diseases. The clinical translation of mRNA therapeutics has been made possible through advances in the design of mRNA manufacturing and intracellular delivery methods.

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Nucleotides Modifications

Mon, 29 Nov 2021 08:39:21 GMT

Nucleotides modifications affect a diversity of biological processes in the organisms. For instance, modifications (commonly N⁶-methyladenosine) in messenger RNA (mRNA) regulate various aspects, such as mRNA location, metabolism, stability, protein translation, even stem cell differentiation. Chemical modifications in tRNA and rRNA directly affect protein translation. In humans, these diverse modifications in RNAs are closely linked to some human disorders, such as tumors and cancers, neurological disorders, mitochondrial-linked diseases, and diabetes.

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mRNA 5' Capping

Mon, 29 Nov 2021 08:38:09 GMT

All eukaryotic mRNA consists of a cap structure, an N7-methylguanosine, which is connected to the first nucleotide of the RNA by a reverse 5' to 5' triphosphate linkage. In addition to the important role of its cap-dependent protein synthesis promoter, the mRNA cap also serves as a protective group for exonuclease cleavage of 5' to 3' nucleic acids, and is the unique identifier for the recruitment of protein factors for pre-mRNA splicing, polyadenylation and nuclear output. It also functions as an anchor for the recruitment of promoters that initiate protein synthesis and the 5' to 3' looping of mRNA during translation. The mRNA 5ʹ cap regulates splicing, nuclear output, resistance to exonuclease degradation, and initiation of translation.

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Custom mRNA Modification

Mon, 29 Nov 2021 08:35:50 GMT

During the past years, the mRNA-based therapy which is founded on the induction of the transient translation with the cell's ribosomes of fully functional proteins without integration into the host genome has become a potential drug for cancer immunotherapy and prophylactic vaccines. Compared with conventional gene therapy and protein substitution strategies, in vitro synthetic (IVT) mRNA has several advantages. However, the molecule's instability and immunogenicity caused by the lack of a cap structure at the 5' end and a long sequence of polyadenylate residue (poly(A) tail) at the 3' end hamper the development of mRNA therapeutics for many years. As the cap structure and the poly(A) tail of the mRNA greatly enhance the stability of natural mRNA, synthetically produced mRNA can also be modified to contain these structures. Using these modifications, the stability of synthetic mRNAs can be improved, immunogenicity can be reduced, and the translation efficiency can be increased.

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Quality Control of mRNA Product

Mon, 29 Nov 2021 08:33:45 GMT

During past years, mRNA products have come into focus as a potential new drug class to deliver genetic information. To date, many mRNA-based therapeutics, such as cancer vaccine development and gene therapy therapeutics, have been developed for multiple applications. However, all genetic sequences are susceptible to random mutation. According to the regulatory requirements of the FDA, strict quality control should be conducted in the preclinical phase to assure product safety, identity, quality, purity, and strength (including potency). Moreover, orthogonal analytical techniques should be applied to assess the quality of all components including all materials and components used for the manufacture of a gene therapy product such as vectors, reagents, and excipients.

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Custom IVT Synthesis of mRNA

Mon, 29 Nov 2021 08:32:38 GMT

With the development of IVT methods, synthetic mRNA has become an emerging class of gene therapy. IVT mRNA has several advantages, such as the mRNA does not require nuclear localization to mediate protein translation. The intracellular process for protein expression is much simpler, and the level of protein expression is far enhanced. IVT mRNA can be produced in large-scale amounts in GMP quality, allowing the clinical application of mRNA-based therapies. Due to its safety and high efficiency, IVT mRNA is an especially attractive gene expression system for applications in regenerative medicine, vaccination, cell engineering, and protein replacement therapy.

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Chemical Synthesis of mRNA

Mon, 29 Nov 2021 08:31:38 GMT

Modified mRNAs can readily be obtained from any DNA template using RNA polymerases in a short time. However, mRNA prepared with enzymatic synthesis may present transcriptional errors, which can only be produced at a laboratory scale, and products may not pure enough for the intended use. An efficient scalable non-enzymatic (chemical) method for mRNA production could solve these problems. Chemical synthesis of single-stranded mRNA molecules is a widely used laboratory procedure that is an alternative strategy of mRNA synthesis for RNA research as well as RNA biopharmaceuticals. This technique is versatile and allows the researcher to tailor the synthesis of short fragments of mRNA and introduce modifications to mRNA.

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mRNA Synthesis

Mon, 29 Nov 2021 08:28:09 GMT

Recently, synthesized mRNA has been developed for cell engineering, CRISPR/Cas9 genome editing, prophylactic vaccines, and therapeutics.

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