Developing safe and controllable Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based therapies with design principles of synthetic biology

Abstract

The CRISPR/Cas9 gene-editing tool is currently in clinical trials as the excitement about its therapeutic potential is exponentially growing. However, many of the developed CRISPR based genome engineering methods cannot be broadly translated in clinical settings due to their unintended consequences. These consequences, such as immune reactions to CRISPR, immunogenic adverse events following receiving of adenoassociated virus (AAV) as one of the clinically relevant delivery agents, and CRISPR off-target activity in the genome, reinforces the necessity for improving the safety of CRISPR and the gene therapy vehicles. Research into designing more advanced CRISPR systems will allow for the increased ability of editing efficiency and safety for human applications. My work 1Develops strategies for decreasing the immunogenicity of CRISPR/Cas9 system components and improving the safety of CRISPR-based gene therapies for human subjects. 2Demonstrates the utility of this system in vivo for transient repression of components of innate immunity and adaptive and 3Examines an inducible all-in-one CRISPR-based control switch to pave the way for controllable CRISPR-based therapies. Biological Design Doctoral Defense Developing safe and controllable Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based therapies with design principles of synthetic biology Farzaneh Moghadam Advisor: Dr. Samira Kiani July 2, 2020; 2:30 PM; Zoom Link: https://asu.zoom.us/j/99796752850 School for Engineering of Matter, Transport and Energy