Broad star Feng Zhang unveils a new CRISPR platform, editing RNA and eliminating Alzheimer's threat — in cells
Broad Institute star scientist Feng Zhang is back in the spotlight, adapting CRISPR technology in a shift from permanently editing DNA to revising RNA — temporarily if needed. And he illustrated the promise of this approach by deactivating APOE4, which may be a ticking time bomb for people at risk of developing Alzheimer’s.
CRISPR/Cas9 gene editing tech has taken the lab by storm, in part because of the work Zhang and his one-time colleagues Jennifer Doudna and Emmanuelle Charpentier accomplished. They’re still scrapping over the patents to the original Cas9 work. But Zhang, who founded Beam Therapeutics with David Liu and Keith Joung, has moved on in search of better tech, and in a paper published in Science, says they have made real progress in switching from DNA to RNA editing.
They call this new advance RESCUE: RNA Editing for Specific C to U Exchange. And it builds on REPAIR: RNA Editing for Programmable A to I.
Using Cas13, Zhang’s team was able to take the APOE4 gene — believed to carry the added risk of spurring Alzheimer’s — and changed it to a benign APOE2. The RNA editors converted “the nucleotide base adenine to inosine, or letters A to I. Zhang and colleagues took the REPAIR fusion and evolved it in the lab until it could change cytosine to uridine, or C to U.”
But there are also ways to achieve a temporary change that could benefit patients without creating potential risks.
In a separate cell experiment, Zhang and his group were able to orchestrate a transitory spike in β-catenin activation and cell growth. That kind of temporary impact could erase threats of cancer, associated with uncontrolled cell growth while treating wounds.
“To treat the diversity of genetic changes that cause disease, we need an array of precise technologies to choose from. By developing this new enzyme and combining it with the programmability and precision of CRISPR, we were able to fill a critical gap in the toolbox,” says Zhang, the James and Patricia Poitras Professor of Neuroscience at MIT.
It’s an intriguing experiment, but don’t look for the experiment in cells to make the leap into practice anytime soon. MIT’s Jonathan Gootenberg summed it up for WBUR:
“It’s a first step in a very large journey. We’re still at the base of the mountain, you might say.”