APOBEC3-mediated hypermutation of retroviral vectors produced from some retrovirus packaging cell lines.

Publication Type:

Journal Article

Source:

Gene therapy, Volume 18, Issue 5, p.528-30 (2011)

Keywords:

2011, Animals, Cell Line, Cell Line, Tumor, Center-Authored Paper, Cytosine Deaminase, Fibrosarcoma, Gene Transfer Techniques, Genetic Vectors, Genomics Core Facility, Human Biology Division, Humans, MICE, mutagenesis, Retroviridae, Shared Resources

Abstract:

APOBEC3 proteins are packaged into retrovirus virions and can hypermutate retroviruses during reverse transcription. We found that HT-1080 human fibrosarcoma cells hypermutate retroviruses, and that the HT-1080 cell-derived FLYA13 retrovirus packaging cells also hypermutate a retrovirus vector produced using these cells. We found no hypermutation of the same vector produced by the mouse cell-derived packaging line PT67 or by human 293 cells transfected with the vector and retrovirus packaging plasmids. We expect that avoidance of vector hypermutation will be particularly important for vectors used in gene therapy, wherein mutant proteins might stimulate deleterious immune responses.