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Translation-dependent degradation of <i>cas12</i> mRNA triggered by an anti-CRISPR

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Why This Matters

This research uncovers how the degradation of cas12 mRNA is influenced by translation processes and can be triggered by anti-CRISPR molecules, offering insights into gene regulation and potential improvements in CRISPR-based technologies. Understanding these mechanisms is crucial for developing more precise gene editing tools and combating anti-CRISPR resistance. The findings have significant implications for both the development of safer gene therapies and the advancement of synthetic biology applications.

Key Takeaways

We thank members of the Bondy-Denomy laboratory and C. Gross laboratory for thoughtful discussions; K. Watters for providing plasmids; J. Peters and A. Buskirk for reagents and technical advice; M. Paredes and D. Le for preparing the media used in this work; and K. Lynch for providing us with the necessary facilities and equipment to perform radioactivity experiments. Sequencing was performed at the UCSF CAT. This work was supported by the US National Institutes of Health (R01GM127489), the Vallee Foundation and the Searle Scholarship, and the Defense Advanced Research Projects Agency (DARPA) award HR0011-17-2-0043. The views, opinions and/or findings expressed are those of the authors and should not be interpreted as representing the official views or policies of the Department of Defense or the DARPA Safe Genes program (HR0011-17-2-0043). N.D.M. was supported by the National Institutes of Health awards F32GM133127, K99GM143476 and R00GM143476. M.G. was funded by the Federal Ministry of Research, Technology and Space of Germany under the Microbial Stargazing project (ref. 01KX2324). J.V. was supported by the Gottfried Wilhelm Leibniz Award (DFG Vo875‐18) and SPP2330 (DFG Vo875‐23/2). J.V. is a member of the DFG Cluster of Excellence NUCLEATE for Nucleic Acid Sciences and Technologies (Project-ID 533767322 – EXC 3113/1).