Podcast: How ‘anti-CRISPR’ viral proteins can fine-tune gene editing in medicine and agriculture

Fueled by a new toolbox of powerful DNA manipulation techniques, the gene-editing revolution has accelerated discovery in both medicine and agriculture, rapidly expanding food production and yielding new therapies for life-threatening diseases. The “Cas” series of enzymes (as in CRISPR-Cas9) are the core machinery of the best-known gene-editing process. Now, scientists are identifying new molecules known as “anti-CRISPRs” that could be used to fine tune the function of Cas enzymes for a variety of important applications.

Put briefly, anti-CRISPRs are proteins capable of halting the action of gene-editing machinery. Many viruses use these molecules to disarm the immune systems of bacteria that rely on CRISPR to fight off infection. Researchers hope to exploit this viral countermeasure to regulate gene editing and minimize unintended mutations that can occur during the editing process. According to University of Toronto Biochemist Karen Maxwell, this could have important therapeutic uses:

In genome editing applications, anti-CRISPRs may provide a valuable ‘‘off switch’’ for Cas9 activity for therapeutic uses and gene drives. One concern of CRISPR-Cas gene editing technology is the limited ability to control its activity after it has been delivered to the cell …. which can lead to off-target mutations.

Anti-CRISPRs can potentially be exploited to target Cas9 activity to particular tissues or organs, to particular points of the cell cycle, or to limit the amount of time it is active …. Anti-CRISPRs may also prove to be a useful addition to …. the treatment of bacterial infections. Because many human pathogens encode CRISPR-Cas systems, phages [viruses] used for gene therapy could be outfitted with a variety of anti-CRISPRs to expand their host range and prevent the bacterial adaptive immune response from being mounted.

Microbiologist Joseph Bondy-Denomy and his lab at the University of California, San Francisco are at the forefront of anti-CRISPR research. The team has done important work revealing how viruses use anti-CRISPRs to inactivate Cas enzymes. On this episode of Talking Biotech, Bondy-Denomy joins plant geneticist Kevin Folta to offer an introduction to anti-CRISPR research and explain how it could impact the future of gene editing.

Joseph Bondy-Denomy is a professor in the Department of Microbiology and Immunology at the University of California, San Francisco. Visit his website and follow him on Twitter @joebondydenomy

Kevin M. Folta is a professor in the Horticultural Sciences Department at the University of Florida. Follow professor Folta on Twitter @kevinfolta and email your questions to [email protected]

The Talking Biotech podcast, produced by Kevin Folta, is available for listening or subscription:

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