CRISPR Augmentation of Host Defense and T-cell Targeting

In work originally supported by the Defense Advanced Research Program Administration (DARPA), we are using the CRISPR Cas13d RNAse to specifically degrade viral and host RNA and CRISPRa, in which catalytically inactivated CAS proteins are fused to transcriptional activator proteins for targeting viral infection of respiratory tract epithelial cells. A major goal is for targeting epidemic/pandemic respiratory viruses, such as influenza A virus and SARS-CoV2 for both the prophylaxis and treatment of established infection.  

As part of developing in vivo delivery systems for these anti-viral studies, we discovered that some of these systems also deliver CRISPR Cas protein/guide RNA complexes or other protein cargo to T cells. With the support of the Naddisy Foundation Professorship of Pediatric Food Allergy, Immunology, and Asthma and the Sean M Parker Center for Allergy and Asthma Research, we are currently using this approach for the development of CRISPR-based approaches to target T helper 2 (Th2) immune responses. These immune responses play an essential role in the development of severe allergies to food and environmental allergens and the development of this type of therapy has potential application to many other diseases involving the immune system.