Current gene therapy techniques face critical challenges to translation including targeting incorrect cells, adverse immune reactions, manufacturing cost, and risk of permanently altering a patient’s germline DNA. The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) system is paving the way for therapeutic and investigational gene editing, and modulation in a variety of organisms. As CRISPR pushes forward to the clinic, the design and implementation of control and safety measures are imperative. However, efforts in this space have been limited so far. Here, I will introduce health-related safety concerns associated with using CRISPR and present our research to minimize the risks. I will discuss the application of synthetic biology to generate synthetic gene circuits and address the controllability of CRISPR-based gene therapies. I will demonstrate that CRISPR’s multi-functionality can be employed to generate safety switches in vitro and in vivo. Further, I will discuss our strategy to detect and reduce the immunogenicity of Streptococcus Pyogenes Cas9 in human. Lastly, I will discuss the wider implications of the genomic revolution in future societies and present modalities to engage the public in such conversations.
Engineering Strategies for Safer and Controllable CRISPR-Based Gene Therapies
Assistant Professor, School of Biological and Health Systems Engineering
Arizona State University
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