Exciting new research funded by FPWR has brought us one step closer to an effective gene therapy for Prader-Willi syndrome (PWS). Led by Dr. Charles Gersbach, a pioneer in CRISPR technology at Duke University, a team of biomedical engineers has identified and activated a master epigenetic switch to turn on the silenced PWS region of chromosome 15. This finding underscores the potential of epigenome editing as a powerful approach to correcting genetic deficiencies in PWS and other genetic disorders.
Over time, scientists have adapted CRISPR technology to allow the editing of DNA in human cells. In this case, the Duke team modified CRISPR to activate genes in the PWS region of maternal chromosome 15. These genes are present but silent in all individuals with PWS, regardless of genetic subtype. By restoring the expression of these genes through epigenome editing, researchers aim to correct the underlying genetic changes that lead to PWS.
A key aspect of this research was the extensive analysis of how gene silencing and activation are controlled in the PWS region. While Gersbach and his team have already demonstrated specific methods for silencing
The team tested different CRISPR-based strategies to determine which methods were most effective in achieving sustained gene activation. In the end, they successfully developed two CRISPR strategies capable of activating these silent genes, with a particular focus on achieving long-term reactivation—an essential component of a future gene therapy that may need to last a lifetime.
This study also highlights FPWR’s vital role in funding and advancing resources for the PWS research community and facilitating collaboration that drives innovative research forward. Dr. Gersbach’s team used a series of engineered PWS cells developed and characterized by the Talkowski lab with funding from FPWR, forging a new partnership between these two powerhouse groups.
While work remains before a CRISPR-based gene therapy for PWS becomes a reality, this research represents an important milestone in understanding how to regulate gene expression in the PWS region. Future studies will be needed to demonstrate that gene activation in animal models or human cells can effectively correct PWS characteristics and improve clinical outcomes.
We are incredibly grateful for the dedication of Dr. Gersbach’s team, including Dahlia Rohm, who completed her PhD through this research. Their hard work has laid the foundation for future breakthroughs in PWS gene therapy.
For more details about this exciting project, check out Duke University’s news article: 'Activating Complex Regions of the Genome to Treat Rare Diseases.' For those interested in the full scientific study, you can read the original research, 'Activation of the imprinted Prader-Willi syndrome locus by CRISPR-based epigenome editing' published in Cell Genomics, February 2025.
