Shutting Down the Extra Chromosome in Down’s Syndrome Cells

Ed Yong in Not Exactly Rocket Science:

Many genetic disorders are caused by faulty versions of a single gene. In the last decade, scientists have made tremendous strides in correctingthese faults through “gene therapy”—using viruses to sneak in working versions of the affected genes.

But some disorders pose greater challenges. Down’s syndrome, for example, happens when people are born with three copies of the 21stchromosome, rather than the usual two. This condition, called trisomy, leads to hundreds of abnormally active genes rather than just one. You cannot address it by correcting a single gene. You’d need a way of shutting down an entire chromosome.

But half of us do that already. Women are masters of chromosomal silencing.

Women are born with two copies of the X chromosome, while men have just one. This double dose of X-linked genes might cause problems, so women inactivate one copy of X in each cell.

This is the work of a gene called XIST (pronounced “exist”). It produces a large piece of RNA (a molecule closely related to DNA) that coats one of the two X chromosomes and condenses it into a dense, inaccessible bundle. It’s like crunching up a book’s pages to make them unreadable and useless. XIST exists on the X chromosome, so that’s what it silences. But it should be able to shut down other chromosomes too, if we could just insert it into the right place.

That’s exactly what Jun Jiang from the University of Massachusetts Medical School has done: she used XIST to shut down chromosome 21.

More here.