Gene therapy allows us to treat "incurable" diseases and bring new ideas for other diseases. At present, the main application scenario of gene therapy is the treatment of rare diseases. With the continuous maturity of AAV delivery system, the characteristics of "one dose" of gene therapy are becoming more and more attractive to patients, and more and more pipelines in research are expanding the application scenarios from rare diseases to common diseases.

At present, more than 70% of the gene delivery drugs are delivered by AAV vector, and the genes or genome delivered by AAV will not be integrated into the autologous genome. Therefore, the genes delivered by AAV may be continuously diluted with cell division, death or other causes, resulting in unsustainable efficacy. So the durability of gene therapy has always been a lot of concern.

Gene therapy has become a battleground for the pharmaceutical giants because of its bright prospects and huge commercial potential.

Introduction to gene therapy

Gene therapy is a method that uses gene therapy vector to transduce exogenous therapeutic genes to cells, and then change the original gene expression of cells through the transcription and translation of exogenous genes to treat diseases. The mode of action generally includes:

① Replace the pathogenic gene with the normal gene;

② Inactivation of pathogenic genes;

③ Import of new or modified genes.

 At present, the gene therapy products that are marketed and in clinical trials mainly target tumors, rare genetic diseases and other indications.

Gene therapy is a new generation of precision therapy after small molecule and macromolecule targeted therapy, which provides new treatment concepts and means for tumors, rare diseases, chronic diseases and other refractory diseases, and has long-term and curative effects that may not be matched by general drugs.

Mechanism of action of gene therapy

Gene therapy is a treatment that delivers functional genes to a patient to correct or replace the healing genes. In this treatment, the target gene is introduced into the target cell (target cells), which either integrates with the host cell (host cell) chromosome as part of the host genetic material, or does not integrate with the chromosomes, but can be expressed in the cells, playing a role in treating diseases.

virus vector

 There are currently two solutions to the delivery of gene therapy: mechanical and physical delivery and carrier-based gene delivery. Non-viral vector delivery is mainly considering the safety, therapeutic DNA capacity and cost of viral vectors. At present, non-viral vectors include plasmids or naked DNA (non-viral) and LNP delivery system, etc. However, poor transfection effect and excessive toxicity seriously restrict the clinical transformation of non-viral vectors. Viral vectors include the commonly used adeno-associated virus AAV, lentiviral LV, and retroviral RV.

High quality virus vectors should have sufficient space to deliver large segments of therapeutic genes; have high transduction efficiency, can infect dividing and non-dividing cells; can target specific cells and can stably express transgene for a long time; have low immunogenicity or pathogenic, without causing inflammation; and have the capability of mass production. The n artificially modified virus is currently the most commonly used vector in gene therapy. The optimization and upgrading of viral vector runs through the whole history of gene therapy, and the use of viral vectors with higher infection efficiency and better safety is also the key driver for the success of gene therapy in recent years.

sum up

Gene therapy has become one of the world's most promising field of medicine, although the gene therapy industry is still in the early development, all aspects are not perfect, but with the expansion of future indications, expanding market broadening, the mature technology of cost reduction and health care payment conditions mature, gene therapy prices will gradually decline benefit more patients, therapeutic potential will continue to release, become a huge market tension innovation medical methods. Institutions involved in the related fields of cell and gene therapy jointly promote the development of gene therapy through acquisition, cooperative development, and independent research, so that gene therapy has gradually moved towards the golden track of rapid development.