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Dissecting the mechanism of CRISPR–Cas technologies to design efficient biotechnologies

Nature Structural & Molecular Biology (2024)Cite this article

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CRISPR–Cas enzymes have enabled us to manipulate the genetic code with unparalleled precision and efficiency. Here I explore the structural and biochemical intricacies that govern the functionality of CRISPR–Cas technologies, emphasizing the need for a nuanced mechanistic understanding to overcome current limitations and pave the way for safer and more effective genome-editing applications in medicine and research.

CRISPR–Cas enzymes have emerged as a molecular scalpel for scientists and physicians, who are now able to target and manipulate our genetic code efficiently and precisely. Over the past ten years, scientists have leveraged the ability of these enzymes to target specific genomic regions, beginning with cytosine and adenine base editors, and followed by prime and click editing technologies1 that expanded editing to transversion mutations, insertions and deletions. CRISPR-based technologies have made detecting and treating disease, drug and genetic screening, and creating genetically modified crops more accessible than ever before.

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Acknowledgements

This work has been funded by the Vagelos Scholars Program in the Molecular Life Sciences grant at the University of Pennsylvania, the Frances Velay Fellowship by the Panaphil and Uphill Foundations and the NIGMS R01-GM138908 grant to R. M. Kohli at the Perelman School of Medicine. The author thanks R. M. Kohli for his mentorship and Kohli laboratory members for their support and motivation.

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  1. Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Jasleen Gill

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  1. Jasleen Gill
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Correspondence to Jasleen Gill.

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Nature Structural & Molecular Biology thanks Tian-Min Fu for their contribution to the peer review of this work.

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Gill, J. Dissecting the mechanism of CRISPR–Cas technologies to design efficient biotechnologies. Nat Struct Mol Biol (2024). https://doi.org/10.1038/s41594-024-01366-8

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