CRISPR/Cas systems originally evolved as bacterial adaptive immune systems that protect bacteria from infection by bacterial viruses or phages. In Type II CRISPR/Cas systems, a single effector protein, called Cas9, is diverted to DNA targets by two small RNAs, the tracRNA and the crRNA, that serve as guide RNAs. These two RNAs can be combined into a single guide RNA (sgRNA) that can effectively direct Cas9 to DNA targets and induce its cleavage in not only bacterial but also mammalian cells as well. There have been many proposals about how CRISPR/Cas could be used to promote human health, including the destruction of pro-oncogenic genes, or the repair, by homologous recombination, of genes leaving inactivating mutations.
Our focus is on the use of CRISPR/Cas to target and destroy pathogenic human DNA viruses including HBV, HPV and HIV-1. To this end, we have been developing improved dual vectors, based on different Cas9 proteins encoded by different bacteria, and have now shown effective cleavage and repression of several DNA viruses in cultured cells. We hope to move these studies into animal models in the very near future to see if we can cure animals bearing, for example, an HPV-16 induced tumor, or with a high level HBV infection of their liver.