(233g) Targeting Specific Cell Types With Engineered Lentivirus In Vivo

To date, most of the clinical trials for curing genetic diseases involve engineering specific cells types ex vivo and then transplanting back the modified cells. However, this process is both time-consuming and expensive. Thus, targeting specific cell types in vivo holds great potential for future clinical applications. Recently, our lab has developed a method for targeting specific cells via the engineered lentivirus in vivo (Yang et. al., 2006, PNAS 103:11479-11484). Most labs so far have focused on inserting antibodies or antibody binding domains into the wild type virus glycoprotein. However, it has resulted in low viral titer or unspecific binding. Our approach is to uncouple the wild type lentivirus envelope protein into two different proteins. One is capable of triggering pH-dependent fusion and the other one is responsible for antibody mediated targeting. We have further identified the limiting step of our targeting strategy to be the pH-mediated fusion and have engineered it to be less pH sensitive. In this experiment, we have used B cell lymphoma as our target cell model and generated a cell line carrying a B cell lymphoma antigen (CD20). It has been shown both in vitro and in vivo that enhanced targeting can be achieved by our engineered fusiogenic molecules. Our next step is to apply this technique in a tumor killing experiment by delivering the suicide gene (Thymidine Kinase) into CD20+ cells lines in vivo and subsequently injecting GCV to kill the CD20+ cells.

Reference: Yang, L., Bailey, L., Baltimore, D., & Wang, P. (2006) Proc. Natl. Acad. Sci. USA 103, 11479-11484.