Interdisciplinary Initiatives Program Round 10 - 2020

Guosong Hong, Materials Science & Engineering
Michael Lin, Neurobiology and Bioengineering
Wendy Gu, Mechanical Engineering

A revolution in the treatment of genetic diseases is underway, catalyzed by the discovery of sequence-specific gene editing by the protein Cas9 and its engineered derivatives. However, our current lack of ability to control Cas9 spatially or temporally in the body leads to off-target genome modifications, thereby preventing its application in genetic diseases where gene editing may otherwise be the only effective treatment. Here, we propose to address this challenge by developing an ultrasound-controlled gene editing approach via photoswitchable CRISPR-Cas9. This approach leverages the ultrasoundinduced light emission method recently developed by the Hong lab, understanding of the mechanoluminescence mechanism by the Gu lab, and the photoswitchable CRISPR-Cas9 protein developed by the Lin lab. By combining tissue-penetrant ultrasound and the unique sound-to-light conversion properties of nanomaterials with cutting-edge genetic engineering techniques, our proposed ultrasound-controlled CRISPR-Cas9 system will have therapeutic applications in the treatment of human genetic diseases due to its reduced invasiveness and high spatiotemporal precision.