Packaging Cell Lines for Lentiviral Vector Products

DESCRIPTION (provided by applicant): HIV-1 based lentiviral vectors are becoming an increasingly attractive means of integrating transgenes into target cells. Vectors are in or enterning clinical trials for a diverse group of ailments, including genetic disease, AIDS and cancer. To expand the range of target cells beyond that of HIV-1 (CD4+ cells), vectors are pseudotyped with various viral envelopes. Rimedion has identified the Ross River Virus (RRV) and the feline RD114 envelope glycoproteins to be promising candidates for production of stable packaging cell lines. In this STTR application, Rimedion and its research partner, Indiana University School of Medicine proposes to develop novel, stable lentiviral packaging cell lines using these envelope. These lines will be useful for further preclinical development and will also be suitable for future clinical use. Specific Aim 1: Rimedion will generate stable packaging lines expressing the RRV and RD114 envelopes. Specific Aim 2: Using the packaging cell lines for RRV and RD114, generate stable lentiviral producer cell lines expressing the Green Fluorescent Protein to be used for studies of vector titer, long-term cell line stability and replication competent lentiviral testing. These cell lines will replace the current manufacutring methodolgy (transient transfection) for lentiviral vectors which is not suitable for large scale productions and limits the potential of lentiviral vectors from achieving licensure by the FDA. If successful, these cell lines will provide the platform technology for a large group of new biologic agents. Phase II will include the certification to meet FDA Guidances so the lines may be used in Good Manufacturing Practices. As part of Phase II, the RD114 cell line would be used to create a producer cell line for treatment of adenosine deaminase deficieny in a Phase I clinical trial. Through appropriate material agreements, the lines will also be made available to academic investigators for investigational, non-commerical use through NIH sponsored programs such as the National Gene Vector Biorepostory. PUBLIC HEALTH RELEVANCE: Gene therapy mediated by lentiviral vectors is now in clinical trials and holds promise for a wide variety of genetic diseases, AIDS and cancer. A major limitation to commercialization of these biologic products is large- scale production technology. Rimedion proposes to generate a series of lentiviral packaging cell lines that will allow manufacturing of lentiviral products suitable for FDA licensure specifications.