Strategies of transcriptional regulation in retrovirus production and expression

Abstract

Gene therapy is a promising, yet elusive, method of treatment that may prove capable of halting tumor progression. Retroviral vectors have been developed as gene transfer agents since they are safe, do not elicit an immune response and are easily modified. Continued study and development of these vectors is necessary in order to overcome difficulties associated with virus production and expression. I plan to develop a virus producing system that will protect the virus producing cell line from the affects of a virally encoded cytostatic or cytotoxic gene and avoid mutation to that gene, yet permit growth of these cells in large quantities and for extend periods of time. This will be accomplished by the development of an inducible virus production system. The second area of this project is to develop a retroviral vector that has targeted and enhanced in vivo expression. I plan to develop retroviral vectors that contain modified regulatory elements in the U3 region of the LTR such that viral expression will be directed by factors characteristic of the target cell (targeted expression) of by a factor encoded in the virus itself (enhanced expression). A future aim of this project is to combine these ideas for virus production and expression. If successful, these modifications of retroviral production and expression may be developed for clinical trials for the treatment of cancer. (AU)