In the decade since, CRISPR-Cas9 has spun off multiple variants, expanding into a comprehensive toolbox that can edit the genetic code of life. To Dr. Jennifer Doudna, who won the Nobel Prize in 2020 for her role in developing CRISPR, we’re just scratching the surface of its potential. If the 2010s were focused on establishing the CRISPR toolbox and proving its effectiveness, this decade is when the technology reaches its full potential.
We’ve spilt plenty of ink on CRISPR advances, but it pays to revisit the past to predict the future-and potentially scout out problems along the way. One early highlight was CRISPR’s incredible ability to rapidly engineer animal models of disease.
CRISPR rapidly established dozens of models for some of our most devasting and perplexing diseases, including various cancers, Alzheimer’s, and Duchenne muscular dystrophy-a degenerative disorder in which the muscle slowly wastes away.
CRISPR also accelerated genetic screening into the big data age. A crowning achievement for CRISPR was multiplexed editing. CRISPR can help select for multiple traits or even domesticate new crops in just one generation.
To the authors, we need to further boost CRISPR’s effectiveness and build trust. Here, platforms to rapidly evolve Cas enzymes, the “Scissor” component of the CRISPR machinery, are critical.
There have already been successes: one Cas version, for example, acts as a guardrail for the targeting component-the sgRNA “Bloodhound.” In classic CRISPR, the sgRNA works alone, but in this updated version, it struggles to bind without Cas assistance.
While already possible with prime editing, its efficiency can be 30 times lower than classic CRISPR mechanisms.
“A main goal for prime editing in the next decade is improving efficiency without compromising editing product purity-an outcome that has the potential to turn prime editing into one of the most versatile tools for precision editing,” the authors said.
Currently, CRISPR is generally used on cells outside the body that are infused back-as in the case of CAR-T-or in some cases, tethered to a viral carrier or encapsulated in fatty bubbles and injected into the body.
There have been successes: in 2021, the FDA approved the first CRISPR-based shot to tackled a genetic blood disease, transthyretin amyloidosis.
A key advance for the next decade, the authors said, is to shuttle the CRISPR cargo into the targeted tissue without harm and release the gene editor at its intended spot.
Finally, CRISPR can synergize with other technological advances, the authors said.
Although further expanding the CRISPR toolbox is on the agenda, the technology is sufficiently mature to impact the real world in its second decade, the authors said. CRISPR has advanced at breakneck speed, and regulatory agencies and the public are still struggling to catch up.
Perhaps the most notorious example was that of the CRISPR babies, where experiments carried out against global ethical guidelines propelled an international consortium to lay down a red line for human germ-cell editing.
Although CRISPR is far more precise than previous genetic tools, it’ll be up to consumers to decide whether to welcome a new generation of human-evolved foods-both plant and animal. These are important conversations that need global discourse as CRISPR enters its second decade.
“Just as during the advent of CRISPR genome editing, a combination of scientific curiosity and the desire to benefit society will drive the next decade of innovation in CRISPR technology,” they said.