Anti-CRISPR Protein Breakthrough Could Make Gene Editing Safer
A Step Forward in Genome Editing Safety
Biomedical science is witnessing a significant improvement in gene editing systems. This is all because of the FDA-approved CRISPR-Cas9-based therapeutic approach. CRISPR, also known as the molecular scissors, is one of the most novel gene editing systems. The primary advantage of this technology is its precision.
Scientists are now capable of cutting the DNA at specific loci and making the necessary changes to correct the DNA sequences. With the help of CRISPR-Cas9, faulty genes are being corrected, thereby enabling a permanent cure for various genetic conditions such as sickle cell disease, muscular dystrophy, and certain types of cancer.
However, one of the significant concerns with the CRISPR system was that once the Cas9 enzyme is activated, it remains active for an extended period. This can potentially cause off-target effects. As a result, there could be multiple unintended cuts that could possibly happen in healthy genes, potentially leading to harmful mutations.
Introducing a Safety Switch for Cas9
Researchers from the Broad Institute, including Ronald Raines and Amit Choudhary, have developed a method to deactivate Cas9 after it has completed its editing function.
This is one of the best approaches to minimize the unintended changes in the DNA sequences. Their solution utilizes an anti-CRISPR protein to rapidly and precisely inhibit Cas9 activity. The findings are published in the Proceedings of the National Academy of Sciences (PNAS) and provide insight into how gene editing is far safer.
Ronald Raines, a chemistry professor at MIT, explained that their approach improves the specificity of genome editing while reducing unwanted side effects.
The LFN-Acr/PA Delivery System
The team developed a tool called LFN-Acr/PA, which efficiently delivers anti-CRISPR proteins into human cells. While natural anti-CRISPR proteins can block Cas9, they often struggle to enter cells due to their size or charge. Traditional delivery methods are slow and less effective for medical use.
LFN-Acr/PA uses a protein component from anthrax toxin to deliver anti-CRISPR proteins in just minutes. Even at very low concentrations, it can shut down Cas9 activity with impressive speed, improving editing precision by up to 40%.
Collaboration and Expertise
The entire anti-CRISPR protein design technology is the result of the combined expertise of multiple scientists. Bradley Pentelute, a chemistry professor at MIT, is an expert in anthrax delivery systems. With the contributions of his work, researchers were able to develop a new anti-CRISPR protein. One more assistant professor, named Choudhary, from the Harvard Medical School, helped in optimizing the therapeutic potential of the compound.
This work is the result of the combined expertise of multiple scientists. Bradley Pentelute, an MIT chemistry professor and expert in anthrax delivery systems, contributed to the design. Choudhary, an assistant professor at Harvard Medical School, focused on optimizing the therapeutic potential of the compound.
Implications for the Future of Gene Therapy
The new anti-CRISPR protein delivery method could be a game-changer for the future of genome editing. By giving researchers the ability to control precisely when Cas9 stops working, treatments can become more predictable and much safer for patients.
With patent applications already filed, LFN-Acr/PA represents a promising step toward more refined CRISPR-based therapies, reducing risks while preserving the powerful benefits of gene editing.
