research summary

If the expression of E6 and E7, which are essential for the development and maintenance of cancer, could be extinguished from HPV-associated cancer cells, these cancers would stop growing or die. Recently developed genome-editing technology, CRISPR/Cas9 system, is a revolutionary technique which makes such therapy possible. We have been looking for the best way to terminate expression of E6 and E7 by editing these genes with CRISPR/Cas9 system. Collaboration with Dr. Izumu Saito (National Center for Child Health and Development) and Tomoko Nakanishi (Microbial Chemistry Research Foundation) who recently succeeded in developing adenovirus vectors which can express both Cas9 nickase and 8 copies of guide RNAs, we are developing a new therapy for HPV-associated cancers. By using Cas9 nickase and the double-nicking strategy, off-target genome editing, which makes clinical application of CRISPR/Cas9 difficult, could be eliminated, and contemporary expression of 8 copies of guide RNAs makes simultaneous double strand beaks of 4 sites in the E6 and E7 region.