Targeted retroviral delivery of DNA is effective but hard to control, and can often prove cytotoxic due to insertional mutagenesis. Now Christopher Baum of the Cincinnati Children's Hospital Research Foundation and colleagues have devised a retrovirus-based delivery system that circumvents this problem.1
The team generated mouse leukemia virus-based vectors in which the retroviral primer-binding site was disabled. "They just contain mRNA," Baum says. "They enter the cell but do not initiate the key aspect of the retroviral life cycle, reverse transcription." Thus, host DNA remains untouched. Instead, the mRNA (in this case, encoding Cre recombinase) is immediately translated into protein, a process called retroviral pseudotransduction.
"People had usually thought the mRNA useless when not converted to DNA in the target cell," Baum says. "The efficiency of this shortcut ... is sufficient to express proteins that can exert a drastic effect, even when being expressed for very short periods of time."
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