The Enhanced Expression Of Therapeutic Proteins By Expanding Of Antigen-specific B Cells In Vivo

Safety and efficiency make up the two critical concerns of gene therapy, of which safety is no doubtable, the first consideration. A practical gene therapy also needs considerable expression of exogenous therapeutic gene. Many factors affect the safety and efficiency of gene therapy, such as therapeutic genes, target cells, gene delivery systems as well as the controllable expression of transgenes, among which the gene delivery systems and target cells are in the central of the context.Currently used gene delivery systems can be divided into two groups:viral and non-viral vector systems. Viral vectors hold the advantage of highly efficient transfection, but come up with severe safety problems. Non-viral vectors are generally safer than viral approaches, but their efficiency is much lower. Increasing the efficiency of non-viral vectors remain a challenge.An alternative way to increase the efficiency of gene therapy without any cost of safety is to expande target cells. By specific amplification of the target cells that has been successfully modified to expresse exogenous therapeutic gene, we may eventually achieve a fold-increase of therapy efficiency. In current gene therapy research, the most frequently used target cell is hematopoietic stem cells. Although hematopoietic stem cells is self-renewable and can develop into many cell types, but they can not sustained and keep their multipotial and other characters in in vitro culture conditions. As come to B lymphocytes, there are many B lymphocytes in the peripheral blood and easy to separate, that is, they are much more and easier to get than hematopoietic stem cells. And under the situmulation of antigen, B lymphocytes can develop into memory B cells,which are long-lived cells like hematopoietic stem cells. Even though, B lymphocytes can not culture for a long time in vitro either. Yet, B lymphocyte can be activated and expanded in vivo, after challenged by its specific antigen.In our study, we took advantage of this characteristic of B lymphocyte, simultaneously expressing an antigen-specific BCR(B Cell Receptor) and the therapeutic gene in the cell. After antigen challenge, we observed the expansion of gene modified B lymphocytes in vivo, more importantly, together with this, an apparent increase of the therapeutic gene expression was detected.