Targeting evolutionary conserved sequences circumvents the evolution of resistance in a viral gene drive against human cytomegalovirus

摘要: Gene drives are genetic systems designed to efficiently spread a modification through population. Most engineered gene rely on CRISPR-Cas9 and were in insects or other eukaryotic species. We recently developed viral drive herpesviruses that into population of wildtype viruses. A common consequence is the appearance selection drive-resistant sequences no longer recognized by CRISPR-Cas9. Here, we analyze cell culture experiments evolution resistance against human cytomegalovirus. report after an initial invasion population, positively selected over time outcompetes However, show targeting evolutionary conserved regions ensures viruses have replication defect, leading long-term reduction levels. This marks important step toward developing effective viruses, especially for therapeutic applications.