28 – Modulating gene regulation to treat gene dosage-associated diseases

Event Time

April 1, 2021 at 5:00 pm


In this video Dr Nadav Ahituv presents Modulating Gene Regulation to Treat Gene Dosage-Associated Diseases

Prof. Ahituv shared his labs work with us on April 1st. Prof. Ahituv is an advisor to two companies working to cure diseases like SYNGAP1: Encoded Therapeutics & Regel Therapeutics. His lab is also part of a team from across UCSF, UC Berkeley & the University of Washington that recently secured a grant from the Weill Neurohub. This grant was to look a haploinsufficencies and SYNGAP1 is one of the explicit targets.

Dr. Ahituv is a Professor in the Department of Bioengineering and Therapeutic Sciences and the Institute for Human Genetics at the University of California, San Francisco. He received his Ph.D. in human genetics from Tel-Aviv University working on hereditary hearing loss. He then did his postdoc, in functional genomics, at the Lawrence Berkeley National Laboratory and the Department of Energy Joint Genome Institute. 

The Ahituv lab is focused on understanding the role of regulatory sequences in human biology and disease. Through a combination of comparative genomic strategies, biochemical assays, regulatory element analysis, human patient samples, mouse and fish genetic engineering technologies, and massively parallel reporter assays they are working to elucidate mechanisms whereby genetic variation within these sequences leads to changes in human phenotypes.


00:00 Welcome and Introduction to the work of Dr Nadav Ahituv

03:10 Overview of talk

04:27 Haploinsufficiency: When one functional copy of a gene is not enough 

09:31 CRISPRa as a therapeutic for haploinsufficiency?

11:13 Sim1, an important obesity gene

14:44 CRISPRa for either Sim1 promotor or enhancer rescues the obesity phenotype

22:23 Can we develop it as a therapeutic?

23:35 Many genes cannot get packaged in an AAV

28:23 Summary

43:43 Q&A