According to breakthrough research, families affected by Down’s Syndrome may one day have the opportunity to alleviate many of the syndrome’s harmful aspects. Regardless of the ethical concerns around this treatment, which we won’t debate here, we think just the approach and mechanism developed within this study are worthy of a shout out.
A cunning group of scientists from the University of Massachusetts Medical School “tested the concept that gene imbalance across an extra chromosome can be de facto corrected by manipulating a single gene, XIST (the X-inactivation gene).” Taking advantage of the genome editing power of zinc finger nucleases, researchers “inserted a large, inducible XIST transgene into the DYRK1A locus on chromosome 21, in Down’s syndrome pluripotent stem cells.”
Here’s what they found:
- “The XIST non-coding RNA coats chromosome 21 and triggers stable heterochromatin modifications, chromosome-wide transcriptional silencing and DNA methylation to form a ‘chromosome 21 Barr body’.” So, incredibly, their novel lncRNA is essentially hijacking the X inactivation machinery at multiple levels and using it on chromosome 21
- “Deficits in proliferation and neural rosette formation are rapidly reversed upon silencing one chromosome 21”, illustrating that these changes aren’t just for show.
“In the short term the correction of Down syndrome cells in culture accelerates the study of cell pathology and translational research into therapeutics, but also for the longer-term, potential development of ‘chromosome therapies,’ which utilize epigenetic strategies to regulate chromosomes, is now at least conceivable. Since therapeutic strategies for common chromosomal abnormalities like Down syndrome have received too little attention for too long, for the sake of millions of patients and their families across the U.S. and the world, we ought to try,” says senior author Dr. Jeanne Lawrence.
“The last decade has seen great advances in efforts to correct single-gene disorders, beginning with cells in vitro and in several cases advancing to in vivo and clinical trials,” says Lawrence. “By contrast, genetic correction of hundreds of genes across an entire extra chromosome has remained outside the realm of possibility. Our hope is that for individuals living with Down syndrome, this proof-of-principal opens up multiple exciting new avenues for studying the disorder now, and brings into the realm of consideration research on the concept of ‘chromosome therapy’ in the future.”
Get your dosage in check over at Nature, August 2013.