CRISPR-based RNA editing – Cas7-11June 8, 2022

While CRISPR technology is often thought of in terms of editing DNA, there have also been recent exciting advances in RNA editing. Editing RNA offers certain advantages especially when it comes to therapeutic applications – while changing DNA is permanent and can be inherited, RNA is a transient molecule so any effects from such a treatment should only be temporary. The technology could lead to treatments for not only inherited genetic disorders but also for temporary states such as infectious diseases.

Last week researchers at the MIT McGovern Institute for Brain Research along with collaborators at the University of Tokyo published[1] the detailed structure of Cas7-11, which is currently one of the most promising RNA-guided RNA-targeting CRISPR effectors. Using insights from the structure, the researchers were able to engineer a compact version of the effector (Cas7-11S). This compact size is critical because Cas7-11S is now small enough to fit in the viral vectors typically used for delivery to cells.

Cas7-11 wasn’t the first RNA-guided RNA-targeting CRISPR effector to be discovered but it luckily lacks the non-specific activity and cell toxicity of others, such as Cas13, making it the first to potentially enable in vivo applications. US and PCT patent applications directed to the initial Cas7-11 technology published earlier this year on March 10th (US 2022/0073891 A1 and WO 2022/051020 A2, both filed July 1, 2021 and claiming priority to U.S. Provisional Applications filed September 2, 2020 and June 9, 2021). Claims in the application relate to compositions that cleave an RNA target comprising a guide RNA that specifically hybridizes to the RNA target, and a Cas7-11 polypeptide, as well as related vectors and cells comprising the compositions and methods of use. Any further patent applications directed to the new and improved compact Cas7-11S likely won’t publish for some months.

[1] DOI: https://doi.org/10.1016/j.cell.2022.05.003

Brian D. Keppler, Ph.D. is a registered Patent Agent in the MVS Biotechnology & Chemical Practice Group. To learn more, visit our MVS website, or contact Brian directly via email.