Multidisciplinary team develops new CRISPR platform for gene therapy

Gene therapy, in conjunction with the disruptive technology called Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), has the potential to revolutionize the treatment of previously incurable eye diseases. But current therapies in the pipeline only target one genetic locus at a time. Now, an interdisciplinary team from the Byers Eye Institute at Stanford and the Stanford Department of Bioengineering has developed a new CRISPR platform with unparalleled capability for multiplexed genome engineering in the retina. Their findings were recently published in Nature Cell Biology.

Through synthetic biology and protein engineering, they developed an optimized CRISPR enzyme known as hyperCas12, which can effectively and simultaneously target many genes by processing numerous CRISPR RNAs for highly precise gene regulation, including gene editing, gene activation and gene repression. This capability could expand the scope of CRISPR gene therapy beyond correcting single gene mutations, to include polygenic and complex diseases, including those with epigenetic causes.

“We believe this system can be broadly useful to the gene therapy field,” said Lucie Guo, MD, PhD, the lead author on the study.

It is rare for a resident who is known to provide meticulous patient care, to simultaneously publish a groundbreaking work at this level. This publication is a testament to how Lucie aims for excellence in both clinics and research. Not only that, but also Lucie’s work hits at the heart of collaboration by bringing together scientists across different departments.

Guo, who is a current resident at Byers, is part of the Stanford Ophthalmology Advanced Research Residency (SOAR) Program. Through SOAR, the department sponsors a full-time research year between PGY-1 and PGY-2 years, where residents develop an active research program to maintain through their clinical training.

Guo, who came to Stanford in 2019, used SOAR as an opportunity to lead an interdisciplinary team of scientists under the mentorship of Stanley Qi, PhD, associate professor of bioengineering and ChEM-H, and Sui Wang, PhD, assistant professor of ophthalmology. Yang Hu, PhD, associate professor of ophthalmology, also contributed to the study. Other authors include co-first-author Jing Bian, PhD, and Alex Davis, Pingting Liu, Hannah Kempton, Xiaowei Zhang, Augustine Chemparathy, Baokun Gu, Xueqiu Lin, Draven Rane, Xiaoshu Xu, and Ryan Jamiolkowski.

“It is rare for a resident who is known to provide meticulous patient care, to simultaneously publish a groundbreaking work at this level,” Qi said. “This publication is a testament to how Lucie aims for excellence in both clinics and research. Not only that, but also Lucie’s work hits at the heart of collaboration by bringing together scientists across different departments.”

“I’m grateful to my mentors, teammates and our department’s exceptional support of clinician-scientists, and I’m eager to build upon these efforts throughout my career toward bringing new therapies for our patients,” Guo said. “This is only the beginning.”