Human serum-resistant retroviral vector particles from galactosyl (alpha 1-3) galactosyl containing nonprimate cell lines

Retroviral vector particles (RVP) which are resistant to inactivation by hu man serum will be needed for many in vivo gene therapy applications, Murine -based producer cell lines generate RVP which are inactivated by human seru m, reportedly due to the presence of the galactosyl (alpha 1-3) galactosyl carbohydrate moiety (alpha Gal) on these and other nonprimate producer cell s and RVP. Consequently, human cells (which lack the alpha Gal moiety) have been developed as producer cell lines for generation of human serum-resist ant RVP. In this study, we report that contrary to earlier reports, the pre sence of the alpha Gal moiety on producer cells and RVP does not necessaril y correlate with cell killing or RVP inactivation by human serum. We show t hat the alpha Gal-positive ferret brain cell line, Mpf, is an excellent bas al cell line for generation of RVP which have titers and serum resistance l evels equal to or greater than RVP produced in human cell lines such as HT1 080. Therefore, packaging cell lines need not be limited to those of human or primate origin for production of human serum-resistant RVP.