‘Epigenome editor’ silences gene that causes deadly brain disorders

_{Image by Robina Weermeijer from Unsplash}

A molecular-editing tool that’s small enough to be delivered to the brain shuts down the production of proteins that cause prion diseases, a rare but deadly group of neurodegenerative disorders.

The system — known as coupled histone tail for autoinhibition release of methyltransferase (CHARM) — changes the ‘epigenome’, a collection of chemical tags that are attached to DNA and affect gene activity. In mice, CHARM silenced the gene that produces the harmful proteins that cause prion disease in most neurons across the brain without altering the gene sequence.

CHARM is the first step towards developing a safe and effective ‘one and done’ treatment for reducing the levels of the disease-causing proteins, says Madelynn Whittaker, a bioengineer at the University of Pennsylvania in Philadelphia. The findings were published today in Science1.

“The system addresses significant challenges faced with previous epigenetic-editing systems,” says Whittaker, who co- authored an accompanying perspective article in Science. Challenges include reducing the toxicity of editing tools and delivering them to cells without compromising their potency, she adds.

Prion...