New Advances in Genome Editing Could Speed This Tool’s March to the Clinic

Today’s update was inspired by a new Nature paper from a team of rock star scientists at MIT. Authors Phil Sharp, Robert Langer, and Vikash Chauhan describe a new innovation for CRISPR-based prime editors that allows these genome-editing tools to be far more precise in their targeting. Their new prime editor, called vPE, makes errors at a “strikingly low” rate that’s 60-fold lower than current prime editors, they report.

There’s so much talk about gene editing and CRISPR these days, and not just in the scientific literature. It’s being written into the plots of books, movies, and TV shows with such frequency that I thought it might be time for a quick primer on what this is, where it came from, and how it works.

CRISPR: A Biological Treasure Trove

To really appreciate CRISPR (if you’re not familiar, it’s pronounced “crisper”), you need to know two things. First, that bacteria get infections just like we do — there’s a whole world of viruses that only target bacteria — and these infections happen a lot. Second, for most of the history of science, researchers assumed that bacteria were too simplistic to have immune systems to fight off these infections.

That’s what makes the discovery of CRISPR so special. Scientists had observed decades ago that bacterial genomes contained short, repetitive sequences, and that these sequences seemed to get longer over time. It wasn’t until about 20 years ago that the research community figured out what these sequences were. In another triumph of nature over human assumptions, it turns out that bacteria do have a type of immune system. If they survive a viral infection, their innate CRISPR mechanism grabs a snippet of the invading virus’s genome and pastes it into their own bacterial genome. From that point on, they carry that information like a mug shot — and if they encounter it again with a new infection, the CRISPR mechanism immediately fires up, destroying the virus.

For bacteria, CRISPR is a highly effective protective response. But scientists exploring the discovery of CRISPR saw something else: a highly optimized biological system designed to grab portions of DNA and paste them into a genome. It was, they realized, the basis for an editing tool that could make changes to genes.

Gene Editing in Humans

For the past 15 years, scientists have figured out how to replicate CRISPR activity outside of bacteria and methodically honed the processes involved to improve the accuracy and efficiency of CRISPR-based gene editing.

In what feels like lightning speed for the biomedical field, CRISPR has already been used to treat patients by editing out disease-causing genetic variants. In 2023, the FDA approved the first CRISPR-based gene therapy — a treatment for sickle cell disease that can dramatically improve the health and quality of life for patients. And earlier this year, as all of you dedicated Salisbury’s Take readers know, a clinical team at the Children’s Hospital of Philadelphia developed a CRISPR therapy and used it to treat a six-month old baby with a rare genetic disease.

While all of this is exciting, it does not mean that gene editing is ready for mainstream clinical use. CRISPR is still relatively early in its development; it will continue to be evaluated, improved, and tested for different diseases. The new Nature publication about a more precise prime editor is a great example of the continuing effort to make gene editing more reliable and robust, paving the way for gene editing technologies that could help more patients in the future.