RNA and Genome editing for treatment of Rett Syndrome

Jonathan Watts, PhD / Erik Sontheimer, PhD / Scot Wolfe, PhD / Anastasia Khvorova, PhD | UMASS Medical School

$2,403,735 AWARDED

This group of investigators from UMASS is addressing MECP2 mutations from both DNA and RNA editing approaches. These researchers are among the world’s leaders in knowledge of RNA chemistry as indicated by the university’s history of accomplishment in this area. In 2006 Craig Mello of UMASS was awarded the Nobel Prize for his work in RNA silencing. UMASS and this group in particular, also have expertise in the now universally-used DNA editing machinery called CRISPR/Cas9. Erik Sontheimer, one of the funded researchers at UMASS co-founded and launched one of the very first CRISPR companies, Intellia.

The group has worked together effectively in the past on other indications and will now put their synergistic capabilities to work for Rett Syndrome.

One part of this project seeks to replace exons 3 and 4 at the DNA level to address 97% of all mutations. This is the DNA version of what Stuart Cobb is doing with RNA trans-splicing and we believe it’s important to pursue both the DNA and RNA options in parallel to ensure all possible therapeutic avenues are tested.

The other part of this project complements what we are funding in the Mandel lab to optimize RNA editing guides for use by the naturally occurring RNA editor in neurons called ADAR. In order to deliver their protein and nucleotide cargoes to cells in the brain, they are also working on developing a novel delivery system that doesn’t rely on a virus.

Importantly, this group recently received a sizable NIH grant from the Somatic Cell Genome Editing program that will expand their platform. RSRT funding will leverage this investment and facilitate applying the learnings specifically to Rett Syndrome.


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