Dr. Jeannie Lee, a leading expert in epigenetics and gene regulation at Harvard Medical School and Massachusetts General Hospital, has been awarded a Blavatnik Therapeutics Challenge Award, including $1 million in funding, to expand her groundbreaking work on reactivating the FMR1 gene — the root cause of Fragile X syndrome. This recognition highlights a bold new strategy that could one day reverse the effects of Fragile X, not just manage its symptoms.
The Blavatnik Award is given to researchers whose work shows strong potential to become transformative, real-world therapies. This prestigious honor builds on years of research funded by FRAXA Research Foundation, which has already produced two innovative approaches to repair the FMR1 gene.
Reactivating the FMR1 Gene: Two Promising Paths
Dr. Lee’s lab has developed not one, but two different ways to reactivate FMR1. The first uses carefully selected small molecules to reverse gene silencing. The second method, which may be even more promising, uses a modified version of the gene-editing tool CRISPR. This "dead" Cas9 system doesn’t cut the DNA but instead creates targeted R-loops, encouraging the cell’s own DNA repair system to contract the abnormal CGG repeat and switch the gene back on.
In simple terms? It’s like guiding the cell to fix the problem itself.
In lab experiments, these approaches have not only restarted FMR1 expression but also restored production of FMRP, the protein missing in Fragile X. And all of this happened in less than two weeks in cellular models.
Turning Lab Discoveries Into Preclinical Therapies
Of course, reactivating a gene in a dish is a long way from delivering a safe, effective therapy to families. But thanks to support from FRAXA and now the Blavatnik Award, Dr. Lee’s team is moving full steam ahead.
FRAXA funding enabled the team to develop these reactivation strategies in neurons derived from Fragile X patient cells. The Blavatnik $1M award will now fund the next crucial step — testing these therapies in mouse chimera models, where human Fragile X neurons are implanted into a mouse brain.
With this funding, Dr. Lee’s team will be able to:
- Model how gene-reactivation therapies could be delivered directly into the brain.
- Study the long-term effects of CGG repeat reduction in a living system.
- Generate critical data to attract biotech investment and prepare for future trials.
"Investors really want to see this work. This award provides the opportunity to model how we could deliver the therapeutic into the brain and achieve excision of CGG repeats."
Jeannie Lee, MD, PhD
Harvard Medical School &
Massachusetts General Hospital
While the Blavatnik Award will advance Dr. Lee’s mouse studies, it does not cover research on human brain organoids, a cutting-edge technology where lab-grown mini-brains mimic human brain function. This is a critical next step because:
- The FDA now accepts organoids as a model in place of traditional animal studies.
- Organoids better replicate human brain function than mice, making them an essential tool for testing curative therapies.
Thanks to the generous donors who have launched FRAXA’s new Curative Therapies Fund, FRAXA will now provide a new grant to launch brain organoid modeling of Dr. Lee’s approach. These complementary studies will offer crucial insights as the field pushes closer to clinical application.
The Power of Backing the Right Science Early
Dr. Lee’s decades of work on X-chromosome inactivation have earned her international recognition, and her expertise in reactivating genes on the X chromosome is unmatched. She has been a FRAXA Investigator since 2016. Dr. Lee’s $1 million Blavatnik Award is more than a win for one lab. It’s a powerful example of how early-stage funding from FRAXA can transform bold ideas into game-changing science.
