Biotech & Health

CRISPR DNA editing may cause serious genetic damage, researchers warn

Comment

CRISPR-Cas9, the gene-editing tool that is currently the darling of biotech and many other fields, may not be quite as miraculous as early tests suggested. A new study finds that what scientists thought of as a scalpel may be more like a felling axe, causing damage hundreds of times what was previously observed.

Before anyone panics and checks out the window for mutated monstrosities, it should be said right away that this isn’t a nightmare scenario by any means: the tool can still be used in many ways safely, and the clinical repercussions of the damage are unexplored. But this unexpected limitation of a tool so widely applied will almost certainly put a chill on its use.

CRISPR, as a quick reminder, is basically a molecule that cleanly and reliably snips bases out of DNA strands paired with a molecule that hunts out a single sequence of bases. Together, they act like a pair of laser-guided scissors.

WTF is CRISPR?

The idea is that by cutting out a handful of bases in a sequence that produces, for instance, sickle cell anemia, you can disable that gene altogether. This has been shown in numerous studies, and although unexpected insertions and deletions (abbreviated “indels”) of a handful of base pairs has been observed, no greater damage has been expected or seen — until now.

It turns out that some CRISPR edits may produce indels at the scale of thousands of bases — more than enough to affect adjacent genes or otherwise interfere with normal genetic operation.

The study published today in Nature, by Michael Kosicki, Kärt Tomberg and Allan Bradley of the Wellcome Sanger Institute, explains that previous research may have never encountered this type of damage simply because, essentially, it never allowed damage at this scale to occur.

The problem isn’t that CRISPR is going wild and producing this damage on its own; instead, the issue is an unexpectedly sloppy repair job by the cell itself.

After a CRISPR snip, lead author Bradley explained in a Nature news writeup, “the cell will try to stitch things back together. But it doesn’t really know what bits of DNA lie adjacent to each other.”

While doing its best to repair the damage with a bit of its own genetic cutting and pasting, it may accidentally substitute hundreds or thousands of base pairs that weren’t there, or cut out similarly sized ranges that were supposed to remain.

Because previous studies often used many copies of the same thousand-pair (or thereabouts) sequence to watch CRISPR in action, the possibility of thousand-pair damage was pretty much absent. It’s only when using much longer and more diverse strands of DNA that these high-volume indels are possible.

“We speculate that current assessments may have missed a substantial proportion of potential genotypes generated by on-target Cas9 cutting and repair, some of which may have potential pathogenic consequences,” reads the paper.

Fortunately, the damage seems to only occur when the job performed by the CRISPR complex is the cutting out of a sequence, leaving it open for the cell to repair. There are other methods that involve replacing or deactivating sequences that should not provoke this reaction. And like many problems in the practical biological sciences, it doesn’t need to be feared and worried about — it needs to be studied and accounted for.

Shondra Pruett-Miller, director of the Center for Advanced Genome Engineering at St Jude’s Children’s Research Hospital, explains this a bit better:

I think the study is interesting and important, but not surprising. The field has seen these types of on-target repair events in the past. Of note, the study was not conducted in clinically relevant cell types. However, the article is important because it reminds us that safety and understanding the potential risks associated with genome editing are paramount before moving into the clinic. Although the Bradley study does shine the light on the potential for unexpected on-target events, it does not negate the immense potential of CRISPR-Cas9.

All the same, having serious genetic damage accompany any part of this revolutionary technique will surely (or at least hopefully) spur inquiry and countermeasures, even if it means tapping the brakes on certain existing therapies, experiments and companies.

More TechCrunch

Featured Article

I’m rooting for Melinda French Gates to fix tech’s broken ‘brilliant jerk’ culture

Women in tech still face a shocking level of mistreatment at work. Melinda French Gates is one of the few working to change that.

20 mins ago
I’m rooting for Melinda French Gates to fix tech’s  broken ‘brilliant jerk’ culture

Blue Origin has successfully completed its NS-25 mission, resuming crewed flights for the first time in nearly two years. The mission brought six tourist crew members to the edge of…

Blue Origin successfully launches its first crewed mission since 2022

Creative Artists Agency (CAA), one of the top entertainment and sports talent agencies, is hoping to be at the forefront of AI protection services for celebrities in Hollywood. With many…

Hollywood agency CAA aims to help stars manage their own AI likenesses

Expedia says Rathi Murthy and Sreenivas Rachamadugu, respectively its CTO and senior vice president of core services product & engineering, are no longer employed at the travel booking company. In…

Expedia says two execs dismissed after ‘violation of company policy’

Welcome back to TechCrunch’s Week in Review. This week had two major events from OpenAI and Google. OpenAI’s spring update event saw the reveal of its new model, GPT-4o, which…

OpenAI and Google lay out their competing AI visions

When Jeffrey Wang posted to X asking if anyone wanted to go in on an order of fancy-but-affordable office nap pods, he didn’t expect the post to go viral.

With AI startups booming, nap pods and Silicon Valley hustle culture are back

OpenAI’s Superalignment team, responsible for developing ways to govern and steer “superintelligent” AI systems, was promised 20% of the company’s compute resources, according to a person from that team. But…

OpenAI created a team to control ‘superintelligent’ AI — then let it wither, source says

A new crop of early-stage startups — along with some recent VC investments — illustrates a niche emerging in the autonomous vehicle technology sector. Unlike the companies bringing robotaxis to…

VCs and the military are fueling self-driving startups that don’t need roads

When the founders of Sagetap, Sahil Khanna and Kevin Hughes, started working at early-stage enterprise software startups, they were surprised to find that the companies they worked at were trying…

Deal Dive: Sagetap looks to bring enterprise software sales into the 21st century

Keeping up with an industry as fast-moving as AI is a tall order. So until an AI can do it for you, here’s a handy roundup of recent stories in the world…

This Week in AI: OpenAI moves away from safety

After Apple loosened its App Store guidelines to permit game emulators, the retro game emulator Delta — an app 10 years in the making — hit the top of the…

Adobe comes after indie game emulator Delta for copying its logo

Meta is once again taking on its competitors by developing a feature that borrows concepts from others — in this case, BeReal and Snapchat. The company is developing a feature…

Meta’s latest experiment borrows from BeReal’s and Snapchat’s core ideas

Welcome to Startups Weekly! We’ve been drowning in AI news this week, with Google’s I/O setting the pace. And Elon Musk rages against the machine.

Startups Weekly: It’s the dawning of the age of AI — plus,  Musk is raging against the machine

IndieBio’s Bay Area incubator is about to debut its 15th cohort of biotech startups. We took special note of a few, which were making some major, bordering on ludicrous, claims…

IndieBio’s SF incubator lineup is making some wild biotech promises

YouTube TV has announced that its multiview feature for watching four streams at once is now available on Android phones and tablets. The Android launch comes two months after YouTube…

YouTube TV’s ‘multiview’ feature is now available on Android phones and tablets

Featured Article

Two Santa Cruz students uncover security bug that could let millions do their laundry for free

CSC ServiceWorks provides laundry machines to thousands of residential homes and universities, but the company ignored requests to fix a security bug.

2 days ago
Two Santa Cruz students uncover security bug that could let millions do their laundry for free

TechCrunch Disrupt 2024 is just around the corner, and the buzz is palpable. But what if we told you there’s a chance for you to not just attend, but also…

Harness the TechCrunch Effect: Host a Side Event at Disrupt 2024

Decks are all about telling a compelling story and Goodcarbon does a good job on that front. But there’s important information missing too.

Pitch Deck Teardown: Goodcarbon’s $5.5M seed deck

Slack is making it difficult for its customers if they want the company to stop using its data for model training.

Slack under attack over sneaky AI training policy

A Texas-based company that provides health insurance and benefit plans disclosed a data breach affecting almost 2.5 million people, some of whom had their Social Security number stolen. WebTPA said…

Healthcare company WebTPA discloses breach affecting 2.5 million people

Featured Article

Microsoft dodges UK antitrust scrutiny over its Mistral AI stake

Microsoft won’t be facing antitrust scrutiny in the U.K. over its recent investment into French AI startup Mistral AI.

2 days ago
Microsoft dodges UK antitrust scrutiny over its Mistral AI stake

Ember has partnered with HSBC in the U.K. so that the bank’s business customers can access Ember’s services from their online accounts.

Embedded finance is still trendy as accounting automation startup Ember partners with HSBC UK

Kudos uses AI to figure out consumer spending habits so it can then provide more personalized financial advice, like maximizing rewards and utilizing credit effectively.

Kudos lands $10M for an AI smart wallet that picks the best credit card for purchases

The EU’s warning comes after Microsoft failed to respond to a legally binding request for information that focused on its generative AI tools.

EU warns Microsoft it could be fined billions over missing GenAI risk info

The prospects for troubled banking-as-a-service startup Synapse have gone from bad to worse this week after a United States Trustee filed an emergency motion on Wednesday.  The trustee is asking…

A US Trustee wants troubled fintech Synapse to be liquidated via Chapter 7 bankruptcy, cites ‘gross mismanagement’

U.K.-based Seraphim Space is spinning up its 13th accelerator program, with nine participating companies working on a range of tech from propulsion to in-space manufacturing and space situational awareness. The…

Seraphim’s latest space accelerator welcomes nine companies

OpenAI has reached a deal with Reddit to use the social news site’s data for training AI models. In a blog post on OpenAI’s press relations site, the company said…

OpenAI inks deal to train AI on Reddit data

X users will now be able to discover posts from new Communities that are trending directly from an Explore tab within the section.

X pushes more users to Communities

For Mark Zuckerberg’s 40th birthday, his wife got him a photoshoot. Zuckerberg gives the camera a sly smile as he sits amid a carefully crafted re-creation of his childhood bedroom.…

Mark Zuckerberg’s makeover: Midlife crisis or carefully crafted rebrand?

Strava announced a slew of features, including AI to weed out leaderboard cheats, a new ‘family’ subscription plan, dark mode and more.

Strava taps AI to weed out leaderboard cheats, unveils ‘family’ plan, dark mode and more