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Deciphering Gene Therapy with Cyagen

Gene therapy introduces a modified gene into diseased cells to treat a genetic-based disease. The new gene usually contains a functioning gene to correct the effects of a disease-causing mutation, which may be either spontaneous or inherited. In the past few decades, gene therapy has made significant progress in the treatment of genetic diseases. In practice, scientists apply genomic and proteomic methods to identify the disease-causing gene, subsequently verifying the target gene with in vitro and in vivo experiments. With this methodology, scientists have published many high-impact gene therapy research articles.

Over the last decade, Cyagen has delivered hundreds of genetically modified animal models and virus packaging services to researchers for gene therapy applications. By the end of 2020, Cyagen’s products and services have been cited in over 4,750 publications across highly reputed peer-reviewed journals, such as Nature, Cell, Science, and more. With our expertise, Cyagen provides guaranteed genetically engineered animal models and viral packaging services for gene therapy research. The use of such models are known to improve clinical transformation of gene therapy.

If you have questions about choosing the right animal models for gene therapy research, please contact at 86 20-31601779 or email for complimentary support, consultations, and project strategy design.

Understanding Gene Therapy

Gene therapies are powerful research tools which deliver nucleic acids into diseased cells to directly treat illness – these are also being tested in human clinical trials for a range of applications. A thorough understanding of the currently available gene therapy methods is critical for successfully developing new gene therapy strategies and projects. Herein, we will discuss 4 gene therapy strategies: gene augmentation, gene silencing/inhibition, genome editing and gene suicide. (Since gene suicide is mainly used to destroy tumor cells with an oncolytic virus, this page will not explore this topic in detail.)


Gene Augmentation

Gene augmentation therapy is used to treat diseases caused by loss-of-function mutations, which prevent the gene from producing a functional product. This gene therapy technique introduces DNA containing a functional version of the lost gene into the cell and aims to produce a functioning product at sufficient levels to replace the protein that was originally missing.

Gene augmentation therapy is the most common treatment option for spinal muscular atrophy (SMA). SMA is caused by a deficiency of a motor neuron protein called SMN1, so the basic concept of gene therapy treatment is to insert the normal SMN1 gene into the diseased cell. Importantly, vector AAV9 can deliver cDNA of SMN1 gene to the cells. The first gene therapy treatment for SMA was approved by the Food and Drug Administration (FDA) in 2019. Despite being an effective option to minimize the progression of SMA and improve survival, this treatment is costly. At present, the commonly used strategies of gene augmentation therapies include delivering of a new protein-coding gene, increasing the expression of growth factors and cytokines, as well as cellular cytokines and autophagy activation of the diseased protein.

If the mutation fragment length of the diseased gene is too large for the vector, one solution is to adopt alternative splicing. The alternative splicing method has achieved great success in Duchenne Muscular Dystrophy (DMD) treatment. Scientists have used antisense oligonucleotides (ASOs) to interfere with the translation of protein mRNA, preventing the mutant exons from being translated, and thereby avoiding the loss of protein function caused by disease-causing nonsense and frameshift mutations.


Gene Silencing

In cases where the addition of a functional gene does not resolve the disease phenotype, gene silencing therapy may be used to shut down (silence) the expression of an abnormal gene. For diseases caused by dominantly inherited disorders, just one abnormal allele can manifest the disease phenotype and related dysfunctionality of cells or organs. A common example is the constitutive expression of oncogene mutations in tumor cells, which requires gene therapy to inhibit the function and expression of pathogenic genes. RNA interference (RNAi) therapy has been applied in research across many polyglutamine (PolyQ)-related diseases, including Huntington’s disease (HD) and spinocerebellar ataxias (SCAs), with the aim to reduce the expression of toxic proteins. Although single-stranded ASOs can mediate gene silencing – small/short interfering RNA (siRNA), short hairpin RNA (shRNA), and microRNA (miRNA) therapies typically provide stronger inhibitory function and durability.


Gene Editing

In gene therapy applications, the use of gene editing technology has been closely tied to the development of CRISPR-Cas9 technology, which has made gene editing in organisms much easier and inexpensive. Importantly, CRISPR-Cas9 gene editing technology has become widely used in gene therapy and served as a breakthrough approach to many previous restrictions, such as the limitations by disease type (recessive or dominant disease), gene length, and in vitro or in vivo experimental model development. Those experimental limitations and others could be solved by gene editing (CRISPR-Cas9) technology. Below are four key gene editing strategies for gene therapy:

Gene Editing Applications in Rare Disease Research

More than 80% of rare diseases are caused by genetic disorders. With the development of a gene therapy for a rare disease, it can provide hope of a one-time treatment for numerous rare diseases that currently have no specific therapeutic options.

At present, there are gene editing-based gene therapy R&D pipelines in progress for several rare diseases, including Duchenne muscular dystrophy (DMD), congenital immune deficiency, hepatitis B, hemophilia, and cystic fibrosis.

With Cyagen’s professional gene editing platform, we provide accurate genetic engineering disease models to help researchers explore key information on rare disease mechanisms and potential treatment approaches. Our model services may be customized to support drug development programs more efficiently transition from gene discovery and validation to pre-clinical safety and efficacy evaluations.

>> Check here to learn more about Cyagen Rare Disease Model Program.
Case Study of Gene Therapy-Point Mutation Mice Generation

The research groups of Dr. Bin Zhou (Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences) and Dr. Hefeng Huang (International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University) co-published an article titled "In Vivo AAV-CRISPR/Cas9-mediated Gene Editing Ameliorates Atherosclerosis in Familial Hypercholesterolemia" in the journal Circulation.

In this study, researchers find that adeno-associated virus (AAV) delivers CRISPR/Cas9 to achieve Ldlr gene correction that can partially rescue LDLR expression and effectively ameliorate atherosclerosis phenotypes in Ldlr mutant mice generated by Cyagen. The nonsense point mutation mouse line, LdlrE208X, is based on a gene mutation relevant to familial hypercholesterolemia - providing a potential therapeutic approach for the treatment of patients with the rare disease (Zhao H, Li Y, et al., 2020, Circulation).

Cyagen's Custom Model Capabilities

In under 15 years since its founding, Cyagen has become a leading provider of custom mouse and rat models – delivering over 78,400 models to researchers worldwide and receiving over 4,800 peer-reviewed citations. Cyagen prides itself on its premium customer service: including price-matching, client access to complimentary technical consultations, full confidentiality, and a 100% money-back service guarantee.


Why Choose Cyagen?

1. Complete research solutions – from custom rodent model generation to therapeutic viral packaging and injection.

2. Both in vivo (animal) or in vitro (cell) experimental models available

3. Expert scientific team provides in-depth technical support and assistance in formulating research model strategies.


Cyagen Expert Consultation

If you are engaged with or interested in gene therapy research, Cyagen's experts can provide you with in-depth technical support and discuss your project plans. We also provide customize model generation strategies, helping develop your gene therapy research and publish high-impact articles.


Cyagen's Custom Model Capabilities

From strategy design through to delivery of research-ready custom models, Cyagen offers complete outsourcing for all your animal model needs. We can create any custom mouse or rat model with guaranteed genotype validation, even offering phenotypic characterization and other downstream services required to establish a rare disease model. Our expansive range of products and services include:

Cyagen AI Knockout Mouse Model eBank

Over 16,000 knockout (KO) /conditional knockout (cKO) mouse models are available from the Cyagen AI Knockout Mouse Model eBank with the following advantages compared to other mouse model repositories:

-  Reduced Risk: Validated genome, guaranteed models
-  Skip Backcrossing: 100% pure C57BL/6 background
-  Fast Turnaround: 3,000 live strains, delivered as fast as 2 weeks

Search for your gene of interest >>
Efficient and intelligent Model Customization Platform
Cyagen's TurboKnockout® Gene Targeting service eliminates two generations of breeding, providing founder mice in as fast as 6 months. CRISPR-based Rapid Knockout services enable up to 500kb knockout (KO) and up to 15kb knockin (KI). In terms of facilities, Cyagen has 40.000㎡animal facilities, 25,000㎡specific-pathogen-free (SPF) level animal laboratories, equipped with more than 1,600 IVC feeding equipment, over 150,000 cages, and an animal population capacity exceeding 500,000. From rigorous personnel training, health testing, and genetic control, to personalized breeding and preservation, Cyagen's comprehensive capabilities can meet your every need for customized animal models. Learn more >>
Drug Screening and Assessment Mouse Model Platform
To help domestic researchers easily obtain the highest-quality animal models of disease, Cyagen has established its own drug research and development product line through a combination of self-research and introduction – to serve drug discovery and screening in the fields of cancer, immunity, endocrinology, cardiovasology, neurology, infectious diseases, and more. We are able to provide genetically modified tumor mouse/rat models, Immunodeficient mice, syngeneic model, human tumor cell line xenotransplantation (CDX) model, mice with reconstituted human immune system, immune checkpoint (ICP) humanized mice, models for metabolic disease and drug efficacy evaluations - including obesity, atherosclerosis, diabetes, non-alcoholic fatty liver disease (NAFLD), and more. Learn more >>
One-Stop Small Animal Phenotype Analysis Platform
Cyagen's one-stop small animal phenotype analysis platform can provide standardized phenotyping services covering cardiovascular, tumor, immunity, metabolism, nerve, and other fields. Services include surgical model construction and analysis of blood, tissue histology and morphology, pathology, gene and protein expression, behavioral and metabolic analytics, and more. To provide customers with a complete and systematic service platform, the intermediate work such as model construction, breeding, surgery, model and phenotype analysis are all undertaken by Cyagen – delivering the comprehensive results and final report for use in your study.
Germ-Free Animal Platform
Cyagen has introduced a complete range of germ-free (GF) animal husbandry and testing programs from our partner and leading provider of research models, Taconic Biosciences. Together, we have assembled an excellent germ-free (GF) animal technical team and established a standardized sterile animal feeding and breeding detection technology system. We can provide customers with germ-free (GF) mouse technical services that meet a wide variety of SPF standards as well as after-sales and training services. Learn more >>
Custom Cell Line Services
Cyagen can provide various types of custom cell line services such as vector construction, virus packaging and over expression, interference, gene knockout cell line, point mutation cell line and gene knockin cell line. Leverage our experts and optimized CRISPR/Cas9 cell line modeling service platform CRISPR-Pro for a hassle-free research. CRISPR-Pro enables large fragments excision or correct mutations in various cell lines. Learn more >>


SETD2 Restricts Prostate Cancer Metastasis by Integrating EZH2 and AMPK Signaling Pathways.
Cancer Cell DOI: 10.1016/j.ccell.2020.05.022 (2020) IF=26.602
Dual-targeting Nanoparticle Vaccine Elicits a Therapeutic Antibody Response Against Chronic Hepatitis B.
Nature Nanotechnology PMID: 32123380 (2020) IF=33.407
Reducing Hypothalamic Stem Cell Senescence Protects against Aging-Associated Physiological Decline.
Cell Metabolism PMID: 32004475 (2020) IF=22.415
The Stem Cell Pluripotency Genes Klf4 and Oct4 Regulate Complex SMC Phenotypic Changes Critical in Late-Stage Atherosclerotic Lesion Pathogenesis.
Circulation DOI: 10.1161 (2020) IF=23.054