Researchers have discovered a way to program cells to inhibit CRISPR-Cas9 activity. “Anti-CRISPR” proteins had previously been isolated from viruses that infect bacteria, but now University of Toronto and University of Massachusetts Medical School scientists report three families of proteins that turn off CRISPR systems specifically used for gene editing. The work, which appears December 15 in Cell, offers a new strategy to prevent CRISPR-Cas9 technology from making unwanted changes.
“Making CRISPR controllable allows you to have more layers of control on the system and to turn it on or off under certain conditions, such as where it works within a cell or at what point in time,” says lead author Alan Davidson, a phage biologist and bacteriologist at the University of Toronto. “The three anti-CRISPR proteins we’ve isolated seem to bind to different parts of the Cas9, and there are surely more out there.”
CRISPR inhibitors are a natural byproduct of the evolutionary arms race between viruses and bacteria. Bacteria use CRISPR-Cas complexes to target and cut up genetic material from invading viruses. In response, viruses have developed proteins that, upon infection, can quickly bind to a host bacterium’s CRISPR-Cas systems, thus nullifying their effects.
Anti-CRISPR proteins are attractive experimentally because they offer one solution for preventing potential off-target effects. Research in mice has shown that such mistakes may be rare when using CRISPR-Cas9 technology, but even the occasional error could be a serious problem when being used therapeutically in humans.
“CRISPR-Cas9 in ancillary cells, tissues, or organs is at best useless and at worst a safety risk,” says co-author and collaborator Erik J. Sontheimer, a professor in the RNA Therapeutics Institute at the University of Massachusetts Medical School. “But if you could build an off-switch that keeps Cas9 inactive everywhere except the intended target tissue, then the tissue specificity will be improved.”
“Knowing we have a safety valve will allow people to develop many more uses for CRISPR,” says co-author Karen Maxwell, an assistant professor in biochemistry who is also at the University of Toronto. “Things that may have been too risky previously might be possible now.”
While the work will be of great interest to those studying gene editing and gene drives, Davidson’s team is also curious to follow up on the biology of how bacterial CRISPRs and viral anti-CRISPRs interact.
“We didn’t set out to find anti-CRISPRs, we were just trying to understand how phages incorporate themselves into bacterial genomes and stumbled onto something that I think will be important for biotechnology,” Davidson says.
“We were being observant and following a path that we didn’t know where it could lead, and it’s just been a very fun and exciting story.”
Learn more: An anti-CRISPR for gene editing
[osd_subscribe categories=’crispr’ placeholder=’Email Address’ button_text=’Subscribe Now for any new posts on the topic “CRISPR”‘]
Receive an email update when we add a new CRISPR article.
The Latest on: Anti-CRISPR
[google_news title=”” keyword=”anti-CRISPR” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]
via Google News
The Latest on: Anti-CRISPR
- BLUE vs. CRSP: Why Are These Stocks Moving in Opposite Directions?on May 17, 2024 at 9:46 am
What’s the Difference? Bluebird Bio and CRISPR Therapeutics are frontrunners in gene editing, offering hope for patients battling blood disorders like sickle cell disease (SCD) and beta-thalassemia ...
- CRISPR Therapeutics AG CRSPon May 15, 2024 at 5:00 pm
We sell different types of products and services to both investment professionals and individual investors. These products and services are usually sold through license agreements or subscriptions ...
- We now know Tome’s gene editing targeton May 13, 2024 at 5:41 am
Initially to treat a rare disease called phenylketonuria —To design a natural killer cell therapy heavily engineered to safely treat autoimmune diseases ...
- CRISPR restores some vision to blind patients in clinical trialon May 12, 2024 at 5:00 pm
CRISPR gene-editing has improved the vision of patients with an inherited form of blindness, according to results of a Phase 1/2 clinical trial. The results not only give new hope to patients with ...
- CRISPR edits fail to cure HIV patients in early teston May 9, 2024 at 4:59 pm
BALTIMORE — An ambitious effort to cure HIV with CRISPR genome editing fell short in an early clinical trial, investigators announced Friday morning. In the study, run by Excision ...
- Crispr Therapeutics Q1 Earnings: Casgevy Launch Tip Of Gene Editing Icebergon May 9, 2024 at 6:32 am
Crispr Therapeutics AG shows potential for future earnings with its gene editing therapy Casgevy, offering treatment for various diseases. Read more here.
- Seek Labs Announces Successful Completion of African Swine Fever Virus In Vivo Trial Utilizing CRISPR-based Treatmentson May 6, 2024 at 3:18 pm
Seek Labs, a healthcare innovations company developing next-generation point-of-care molecular diagnostic systems and novel CRISPR-based gene therapie ...
- CRISPR's Molecular Mechanisms for Antibiotic Resistanceon April 28, 2024 at 4:02 pm
This process is governed by several complicated pathways. Bacteria also possess built-in anti-CRISPR systems, that can repair any damage caused by CRISPR-Cas systems. Defense systems that the ...
- CRISPR is promising to tackle antimicrobial resistance, but remember bacteria can fight backon April 25, 2024 at 5:00 pm
This process is governed by several complicated pathways. Bacteria also possess built-in anti-CRISPR systems, that can repair any damage caused by CRISPR-Cas systems. Defence systems that the ...
via Bing News