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Research Strategies


One of the genes known to cause LCA, the CEP290 gene, is critical for the normal functioning of cilia, which are microscopic hair-like structures found in retinal photoreceptors and are necessary for the perception of sensory input, including vision. The most common CEP290 gene mutation in LCA reduces the production of the key ciliary protein CEP290. Researchers at the Li Weibo Institute for Rare Diseases Research are studying the molecular and cell biological bases of LCA, with a focus on uncovering the function of CEP290. Specifically, the Khanna lab is delineating the role of CEP290 in regulating the formation and maintenance of cilia in photoreceptor cells, using a naturally occurring mouse mutant of CEP290. They are also developing treatment strategies, such as nanoparticle and viral vector-based delivery of correct gene counterparts to animal models of LCA. In complementary studies, the Witman lab is elucidating the structure and function of CEP290, using both mouse CEP290 mutants and the unicellular Chlamydomonas, a model organism for cilia-related disease that is amenable to biochemical, genetic, and molecular genetic approaches. These studies are advancing our understanding of the pathogenesis of CEP290-associated retinal degenerative diseases and setting the stage for the development of potential gene therapy for patients with LCA.


Gene therapy using a miniCEP290 fragment delays photoreceptor degeneration in a mouse model of Leber congenital amaurosis

Authors: Zhang W, Li L, Su Q, Gao G, and Khanna H

Published in 2018 in Human Gene Therapy

In gene therapy for retinal diseases, the conventional means to transport a correct gene into the eye uses adeno-associated viral (AAV) vectors. However, the large size of the CEP290 gene has been a roadblock to using these vectors. This study presents a novel gene therapy strategy using a truncated version of the CEP290 gene that can be used with AAV vectors. The results showed that subretinal injection of AAV particles carrying the CEP290 “minigene” into neonatal CEP290 mutant mice significantly improved photoreceptor survival, morphology, and function, compared to control mice. These findings show the potential of using a truncated CEP290 gene as a therapeutic strategy in patients with LCA.


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Leber Congenital Amaurosis Slider Investigators

Hemant Khanna, PhD

Hemant Khanna, PhD

Associate Professor, Department of Ophthalmology & Visual Sciences

Khanna Lab

Guangping Gao, Ph.D.

Guangping Gao, PhD

Co-Director, Li Weibo Institute for Rare Diseases Research, Director, Horae Gene Therapy Center and Viral Vector Core, Professor of microbiology and physiological systems, Penelope Booth Rockwell Professor in biomedical Research

Gao Lab


George Witman, PhD

Professor of Radiology, George F. Booth Chair in Basic Sciences

Witman Lab

Clinical Trials

At the Li Weibo Institute for Rare Diseases Research, our researchers and clinicians are dedicated to finding new treatment options for patients. Our clinical trials program is another way we continue to advance treatments and make new discoveries. If you or someone you know may be interested in a clinical trial, please subscribe for updates and you will be notified when we open up a new trial.