Using CRISPR activation (CRISPRa) to Upregulate the Existing Gene Copies as a Novel Therapy for the Deletion Genotype of Angelman Syndrome

Quick Overview

Dr. Nadav Ahituv presented a new approach using CRISPR activation (CRISPRa) to upregulate existing gene copies as a potential therapy for the deletion genotype of Angelman Syndrome. By targeting specific gene regulatory elements, the CRISPRa technique aims to increase the expression levels of genes that are haploinsufficient, meaning they have only one functional copy. The approach has shown promising results in mouse models for obesity and SCN2A-related disorders, and the team is now working on developing a virus that can upregulate multiple genes simultaneously. The ultimate goal is to provide a potential therapy for the 70-80% of Angelman Syndrome patients with a deletion genotype.

Dr. Nadav Ahituv from the University of California, San Francisco, will be presenting a new approach using CRISPR activation (CRISPRa) to upregulate existing gene copies as a novel therapy for the deletion genotype of Angelman Syndrome. This groundbreaking research aims to provide a potential treatment for individuals with Angelman Syndrome who have a deletion in the UBE3A gene.

Introduction

Dr. Ahituv introduces himself as a geneticist with a passion for understanding and treating genetic diseases. He explains that his research focuses on gene regulatory elements, which are responsible for controlling when and how genes are expressed. He highlights that only 2% of our genome consists of genes, while the remaining 98% is made up of regulatory elements.

Gene Regulatory Elements and Haploinsufficient Diseases

Dr. Ahituv explains that gene regulatory elements, such as promoters and enhancers, play a crucial role in controlling gene expression. Mutations in these elements can lead to human genetic diseases. He specifically focuses on haploinsufficient diseases, where individuals have one functional copy of a gene instead of the usual two. This results in reduced gene expression and can lead to severe health issues.

CRISPR Activation (CRISPRa) as a Potential Therapy

Dr. Ahituv introduces CRISPR activation (CRISPRa) as a potential therapy for haploinsufficient diseases. Unlike traditional CRISPR gene editing, CRISPRa does not involve cutting the DNA. Instead, it modifies the CRISPR molecule to act as a delivery system for activating gene regulatory elements. By targeting specific promoters or enhancers, CRISPRa can increase gene expression and potentially alleviate the symptoms of haploinsufficient diseases.

Experimental Results and Future Directions

Dr. Ahituv presents the results of his research using CRISPRa in mouse models of obesity and SCN2A-related autism. In both cases, upregulating the existing gene copies led to a significant improvement in the phenotype of the mice. He also discusses ongoing collaborations with researchers working on Angelman Syndrome, aiming to upregulate multiple genes affected by the deletion genotype.

Conclusion

Dr. Ahituv concludes by expressing his gratitude to his lab members, collaborators, and funding sources. He emphasizes the potential of CRISPRa as a one-time treatment for genetic diseases and highlights the importance of further research and development to ensure its safety and efficacy. He looks forward to answering questions during the panel discussion.