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Phys Rev Lett. 2021 Nov 12;127(20):208102. doi: 10.1103/PhysRevLett.127.208102.

Search and Localization Dynamics of the CRISPR-Cas9 System.

Physical review letters

Qiao Lu, Deepak Bhat, Darya Stepanenko, Simone Pigolotti

Affiliations

  1. Biological Complexity Unit, Okinawa Institute of Science and Technology Graduate University, Onna, Okinawa 904-0495, Japan.
  2. Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, New York 11794, USA.
  3. Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York 11794, USA.

PMID: 34860046 DOI: 10.1103/PhysRevLett.127.208102

Abstract

The CRISPR-Cas9 system acts as the prokaryotic immune system and has important applications in gene editing. The protein Cas9 is one of its crucial components. The role of Cas9 is to search for specific target sequences on the DNA and cleave them. In this Letter, we introduce a model of facilitated diffusion for Cas9 and fit its parameters to single-molecule experiments. Our model confirms that Cas9 search for targets by sliding, but shows that its sliding length is rather short. We then investigate how Cas9 explores a long stretch of DNA containing randomly placed targets. We solve this problem by mapping it into the theory of Anderson localization in condensed matter physics. Our theoretical approach rationalizes experimental evidence on the distribution of Cas9 molecules along the DNA.

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