Applied Basic Research on Gene Therapy

Gene therapy is the process of preventing or inhibiting the occurrence, progression of diseases by manipulating and intervening at gene level. It is not only a revolution of great consequence in the medical and pharmaceutical fields, but also one of the most important milestones of biomedical development nowadays, and it will surely be the important medical and pharmaceutical industry in 21 century. However, as a whole, the techniques and products of gene therapy are still in the initial development stage, facing many kinds of problems and challenges. The main problems and challenges can be described as follows: firstly, the efficiency of gene transfer systems presently is relatively low, lacking targeting ability; secondly, some gene transfer vectors randomly insert and integrate into the chromosomes of recipient cells, which has the potential danger of insertion mutation and cellular malignant transformation; thirdly, there are still lack of effective methods to regulate the transferred genes. These problems are the main obstacles that restrict the development of effective and safe gene therapy. Consequently, aiming at the problems and challenges that gene therapy facing at present, this project organizes the superior domestic laboratories on gene therapy research and development to investigate targeting gene transfer systems, to explore site-specific gene integration and in situ gene correction, as well as to research regulation of targeting, selective gene expression so that we could make gene therapy more efficiently and safely. We select the severe diseases that threaten human health such as genetic diseases, infectious diseases （especially HIV）, auto-immune diseases, malignant tumors as the study objects, and make great efforts to resolve the key scientific problem of the targeting efficiency of gene therapy. The main contents are as follows: （1）Novel efficient and targeting gene transfer systems: it is mainly to develop a series of novel highly efficient and targeting gene transfer systems, and two peojects of “Research and Development of Novel Viral Gene Delivery Systems” and “Research and Development of Novel Non-viral Vectors and Gene Delivery Systems” are included. （2）The research of site-specific gene integration and in situ gene correction: it is mainly to develop novel technologies of site-specific gene integration and in situ gene correction, and one project of “Site-specific Gene Integration,In situ Gene Correction and Their Mechanisms” is included. （3）The research of targeting and selective expression of therapeutic gene: it mainly investigates kinds of regulators that promote the selective, continuing expression of external genes in the recipient organs or cells, and one project of “Regulation Elements for Targeting, Selective Gene Expression” is included. （4）The exploration of other novel gene therapy strategies, methods, techniques and related mechanisms: one project of “Novel Gene Therapy Technology（Gene Silencing, et al） and Their Mechanisms ” is included. （5）The research of gene therapy of severe human diseases: it selects severe diseases that threaten human health such as genetic diseases, HIV, tumor, auto-immune diseases as the objects of gene therapy, discussing the final effects of gene therapy, as well as testing whether our new techniques, methods and strategies can resolve, or partially resolve the safety and effectiveness of gene therapy. Two projects of “Gene Therapy of Genetic Diseases” and “Immunogene Therapy of Some Important Human Diseases” are included. This project expects that we could have breakthroughs and innovations in the basic theory of gene therapy, break through a set of key techniques, establish some ideal targeting gene transfer systems and gene therapy protocols with state-owned intelligent property rights, and provide a stable and actual basis for gene therapy of genetic diseases, HIV, malignant tumor and auto-immune diseases after five-year hardworks.