Improved method of retroviral vector production for gene therapy
Based on high-level secondary research, current production systems allow for titers of ~106 – 108 functional virus particles per ml of lysate. Neverthe-less, optimization of virus yield may be of interest (i) for economic reasons and (ii) for larger Phase II / Phase III trials.<br><br>
A novel possibility has been found to increase the yield of retroviruses or viral particles thereof from cells by APOBEC4 (Apolipoprotein B mRNA-editing catalytic polypeptide 4) or a modified APOBEC4. APOBEC4 is a human cellular gene belonging to the super family of RNA/DNA editing cytidine deaminases. It could be shown that the presence of N-terminal modified APOBEC4 may increase the yield of retro- or lentiviral vectors produced by a factor of up to 6. <br><br>
Thus, these results position N-terminal modified stabilized APOBEC4 as a new agent to increase the production of retroviral vectors for gene therapy and offer a new interesting approach to identify drugs in a cell-based assay that may suppress HIV replication by suppressing APOBEC4.
<li>The production of retro- or lentiviral vectors can be increased up to 6 fold by modified stabilized APOBEC4 proteins</li>
<li>APOBEC4 inhibitors may be used to suppress HIV replication</li>
European Patent Applic. (06/2007)<br>
PCT Application (06/2008)
Further Information: PDF
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Dr. Dirk Dantz
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