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.
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Acknowledgements
We thank shared resources for DNA sequencing. This work was supported by National Institutes of Health grants UL1 DE19582, a Pilot grant from the Northwest Genome Engineering Consortium (to MJM and ADM); P30 DK47754, a Molecular Therapy Core Center grant (to ADM); and CA09229, a training grant (to MJM).
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ADM is an inventor on several patents describing retrovirus packaging cell lines made using NIH 3T3 cells, including the PT67 cells used in this report. MJM declares no conflict of interest.
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Miller, A., Metzger, M. APOBEC3-mediated hypermutation of retroviral vectors produced from some retrovirus packaging cell lines. Gene Ther 18, 528–530 (2011). https://doi.org/10.1038/gt.2010.177
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DOI: https://doi.org/10.1038/gt.2010.177
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