Department of Molecular, Cell and Cancer Biology; Department of Biochemistry and Molecular Pharmacology; RNA Therapeutics Institute; Program in Molecular Medicine
Computational Biology | Genomics | Investigative Techniques | Nucleic Acids, Nucleotides, and Nucleosides | Therapeutics
The development of robust, versatile and accurate toolsets is critical to facilitate therapeutic genome editing applications. Here we establish RNA-programmable Cas9-Cas9 chimeras, in single- and dual-nuclease formats, as versatile genome engineering systems. In both of these formats, Cas9-Cas9 fusions display an expanded targeting repertoire and achieve highly specific genome editing. Dual-nuclease Cas9-Cas9 chimeras have distinct advantages over monomeric Cas9s including higher target site activity and the generation of predictable precise deletion products between their target sites. At a therapeutically relevant site within the BCL11A erythroid enhancer, Cas9-Cas9 nucleases produced precise deletions that comprised up to 97% of all sequence alterations. Thus Cas9-Cas9 chimeras represent an important tool that could be particularly valuable for therapeutic genome editing applications where a precise cleavage position and defined sequence end products are desirable.
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DOI of Published Version
Nat Commun. 2018 Nov 19;9(1):4856. doi: 10.1038/s41467-018-07310-x. Link to article on publisher's site
Bolukbasi MF, P, Luk K, Kwok SF, Gupta A, Amrani N, Sontheimer EJ, Zhu LJ, Wolfe SA. (2018). Orthogonal Cas9-Cas9 chimeras provide a versatile platform for genome editing. Open Access Articles. https://doi.org/10.1038/s41467-018-07310-x. Retrieved from https://escholarship.umassmed.edu/oapubs/3676
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This work is licensed under a Creative Commons Attribution 4.0 License.