Home Biomedical research Next-generation CRISPR-based drugs are moving faster to the clinic

Next-generation CRISPR-based drugs are moving faster to the clinic


LAfter this year, the now Nobel Prize-winning paper written by Jennifer Doudna and Emmanuelle Charpentier – in which they described how a primordial immune system in bacteria could be exploited to modify the genomes of other organisms – will be 10 years old. The discovery that CRISPR could be turned into an easily programmable tool for DNA rewriting launched biomedical research into the warp engine.

In the 10 years to 2012, 200 articles mentioned CRISPR. In 2020 alone, there were more than 6,000. Over the past decade, scientists have used CRISPR to cure mice of progeria, repair muscular dystrophy in dogs, and eliminate symptoms in people with progeria. genetic blood disorders. Currently, there are more than two dozen human trials of the technology underway around the world.

STAT has created a new tracker of landmark CRISPR studies and found that the explosion of interest has created a positive feedback loop, accelerating the movement of new and better gene-editing approaches to the clinic. For CRISPR 1.0 therapies – those using the original Cas9 cutting enzyme described in Doudna’s article – four and a half years have passed, on average, between the first studies on cells and the first public data on non-human primates. humans. The base edition, or CRISPR 2.0, reduced it to three years, according to the CRISPR TRACKR.


This tendency to save time manifests itself in other ways as well. Last November, Beam Therapeutics announcement he had been given the green light to test his base-editing technology in humans for the treatment of sickle cell disease. If it starts dosing patients this year, it will put Beam a few years behind the CRISPR 1.0 companies – Intellia, Editas Medicine and Crispr Therapeutics – which began clinical studies of therapies for various genetic disorders in 2021, 2020 and 2019, respectively. . , effectively reducing development time from an average of eight years to six.

“We are now seeing a real acceleration of progress,” said Kiran Musunuru, gene editing researcher at the University of Pennsylvania and co-founder of Verve Therapeutics. “As challenges are resolved for 1.0, it’s much easier to replace 2.0, then 3.0, then what’s next.”


The first five years after publication of the seminal papers by Doudna and Charpentier (and by Feng Zhang and George Church), the field was devoted to refining how CRISPR-Cas9 works in different cell types, setting records for the number of cuts he could make, and find medically relevant applications for his targeted gene-severing abilities.

The next five, driven by a gold rush in finding, engineering, or evolving new CRISPR proteins, saw the gene-editing toolkit expand rapidly outward. These newer, brighter, cleaner versions of CRISPR moved faster towards the clinic, propelled by all the groundwork that had been laid by its older, clumsier cousin.

“What is frankly exhilarating to me, as a gray-haired publishing veteran, is the richness of the overall ecosystem,” said Fyodor Urnov, scientific director of the Institute for Innovative Genomics at the Institute. University of California at Berkeley, which is directed by Doudna.

Urnov compared the 2000s, when he and others were working on pre-CRISPR versions of genome editing, to medieval times, with a few labs working in their fiefdoms, separated by vast stretches of no-man’s land. . Tools were few and hard to find. Today, Urnov said, composing a gene-editing experiment is more like clicking open the App Store on your smartphone. Not only will you find options for different types of publishers and delivery modes, but each also comes with ratings and reviews.

“Ten years ago, the ability to just step into this huge assortment of offerings just didn’t exist,” he said.

For many of these tools, it is still too early to tell which will become components of successful therapies and which will run out on take-off. But with the field moving at lightning speed, it won’t be long before we find out.