Gene Therapy Development

Gene is the basic physical and functional unit carrying biological genetic information. It is an intrinsic factor in determining life and health. All life phenomena of organism, such as birth, growth, disease, aging and death, are related to genes. Genetic defects, gene mutation or abnormal regulation of gene expression can cause diseases.

Gene therapy is an experimental technique that introduces genes or short oligonucleotide sequences as therapeutic molecules instead of conventional drug compounds, into human target cells to correct gene defects or play a therapeutic role, so as to achieve the goal of therapeutic purposes. Gene therapy is different from conventional therapy. In general, the treatment of diseases aims at the various symptoms caused by genetic abnormalities, while gene therapy aims at the root cause of diseases—abnormal genes themselves.

Gene vector or gene delivery vehicle is used to introduce genes into cells and can be divided into viral vector such as retrovirus, adenovirus, adenovirus associated virus, lentivirus and non-viral vector such as liposome, receptor and the injection of naked DNA. The target cells of gene therapy are mainly divided into somatic cells and germ cells. Comparing to germline gene therapy, gene modifications in somatic cell gene therapy only affect the individual patient but not inherited by offspring. Therefore gene therapy is limited to somatic cells nowadays while gene therapy of germ cells has many limits, such as a series of ethical issues and technological immaturity.

Figure 1. Vectors used in gene therapy clinical trials. (Ginn, S. L., et al., 2018)

According to the methods of gene manipulation, gene therapy can be divided into the following categories. Gene replacement and gene correction aim at correcting the abnormal sequence of the defective gene by introducing a normal gene to replace the original defective gene that causes disease. Gene augmentation aims at compensating for the function of defective genes by introducing exogenous genes instead of removing abnormal genes to express normal products. Gene inactivation or gene interference aims at inactivating a mutated gene with dysfunction by introducing exogenous genes instead of removing abnormal genes to specifically block the translation or transcription to suppress the expression of some abnormal genes. Two main approaches of these methods are ex vivo modification (in cultured cells extracted from patients who are subsequently transplanted back) and in vivo modification (directly into the patient).

With the breakthrough of gene editing technology and the increase of licensing approval, gene therapy is gaining momentum. Gene therapy is being developed and has made important medical advances to treat several different types of diseases, including cancer, genetic diseases, cardiovascular diseases, infectious diseases, neurological diseases, inflammatory diseases, rare diseases and ocular diseases. However, there are still some unsolved problems of gene therapy including immune response, viral vector problems, complex of multigene disorders, mutagenesis and high cost.

Figure 2. Indications addressed by gene therapy clinical trials. (Ginn, S. L., et al., 2018)

Gene therapy develops in the same way as any other drugs. Preclinical testing of candidate drugs in both in vitro experiments and in vivo in animal models is needed and used to provide proof-of-concept of the drug delivery systems, assess safety, and evaluate efficacy as a guide to dosing in human subjects.

Creative Biolabs provides powerful risk-based preclinical data verification services for gene therapy research and development projects to deal with data reproducibility crisis which is a big obstacle for drug research and development and may lead to failure and high risk of investment. Our combination of expertise in gene therapy and different disease studies as well as comprehensive cell lines and animal models available at Creative Biolabs makes us an ideal partner to support your project and help reduce investment risk—from target validation, hit validation, lead validation, to safety assessment and efficacy evaluation.

Creative Biolabs offers our clients with high quality results by our excellent scientific team and advanced technology platform in a high efficiency and cost-effective manner. Our clients will obtain a complete and reliable project feasibility assessment to help you make reasonable decisions of your project and reduce investment risk. Wise decision-making can also facilitate the project process.

If you need any further information or have any queries about our services, please feel free to contact us and let us know how we can help.

Reference

1. Ginn, S. L., et al., 2018. Gene therapy clinical trials worldwide to 2017: An update. The journal of gene medicine, 20(5), e3015.