shRNA/AAV9 Gene Therapy for the Treatment of Prader-Willi Syndrome

Funding Summary

This research team is exploring a novel approach to activate maternal gene expression from the PWS region of chromosome 15, using a small piece of RNA (short hairpin RNA) to interfere with a protein that silences the maternal chromosome.

Dr. Theresa Strong, Director of Research Programs, shares details on this project in this short video clip. 


Lay Abstract

The maternal copy of PWS genes is intact but silenced by epigenetic regulation, which is normally accomplished by a protein, EHMT2. Dr. Butler and his team have proposed a new method of restoring the maternal copy of the PWS genes by combining two strategies: using a small piece of RNA (short hairpin RNA) to block the functioning of the protein EHMT2, and using an adenovirus vector (AAV) to distribute the short hairpin RNA throughout the whole central nervous system. If this method of gene therapy is successful, it will have several advantages, including maintaining PWS gene expression under the normal regulatory circumstances, and being able to use a one-time administration of the gene therapy. If successful and safe in PWS mice, this method would lead the way into translation into a potential gene therapy for human trials.

Research Outcomes: Public Summary

The findings of our study suggest there is some mechanistic properties of EHMT2 in the regulation of maternal PWS genes. However, directly targeting EHMT2 did not rescue PWS gene transcript levels close to healthy range. Therefore, our findings suggest anti-EHMT2 gene therapy would not be suitable for the treatment of PWS.

Funded Year:


Awarded to:

Ryan Butler, Ph.D.




University of Texas Southwestern


Ryan Butler, Ph.D.

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