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Genetic diversity

Accounting for diversity in the design of CRISPR-based therapeutic genome editing

CRISPR cell and gene therapy have been designed largely with respect to a single reference human genome. A new study reveals how human genetic diversity could lead to off-target effects and presents a new tool to identify these risks.

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Fig. 1: Assaying human genetic diversity can advance the design of human therapeutics involving genome editing.

References

  1. Graham, F. Nature https://doi.org/10.1038/d41586-020-01928-y (2020).

  2. Science News Staff. Science https://doi.org/10.1126/science.adf7363 (2022).

  3. Cancellieri, S. et al. Nat. Genet. https://doi.org/10.1038/s41588-022-01257-y (2022).

  4. Sinha, D. et al. Am. J. Hum. Genet. 107, 278–292 (2020).

    Article  CAS  Google Scholar 

  5. Keough, K. C. et al. Genome Biol. 20, 167 (2019).

    Article  Google Scholar 

  6. Saha, K. et al. Nature 592, 195–204 (2021).

    Article  CAS  Google Scholar 

  7. Misek, S. A. et al. Preprint at bioRxiv https://doi.org/10.1101/2022.11.18.517155 (2022).

  8. Lessard, S. et al. Proc. Natl Acad. Sci. USA 114, E11257–E11266 (2017).

    Article  CAS  Google Scholar 

  9. Scott, D. A. & Zhang, F. Nat. Med. 23, 1095–1101 (2017).

    Article  CAS  Google Scholar 

  10. Leibowitz, M. L. et al. Nat. Genet. 53, 895–905 (2021).

    Article  CAS  Google Scholar 

  11. Maeder, M. L. et al. Nat. Med. 25, 229–233 (2019).

    Article  CAS  Google Scholar 

  12. Musunuru, K. et al. Nature 593, 429–434 (2021).

    Article  CAS  Google Scholar 

  13. Foy, S. P. et al. Nature https://doi.org/10.1038/s41586-022-05531-1 (2022).

  14. Center for Biologics Evaluation and Research. Human Gene Therapy Products Incorporating Human Genome Editing (U.S. Food and Drug Administration, 2022).

Download references

Acknowledgements

K.S. has received funding from the US National Science Foundation, grant nos. EEC-1648035 and AWD-101645-G3/RJ375-G3, and the US National Institutes for Health, grant nos. R35GM119644, U01EY032333 and UH3NS111688.

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Correspondence to Krishanu Saha.

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K.S. receives sponsored research support from Spotlight Therapeutics and Synthego and is an advisor to Notch Therapeutics and Andson Biotech.

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Saha, K. Accounting for diversity in the design of CRISPR-based therapeutic genome editing. Nat Genet 55, 6–7 (2023). https://doi.org/10.1038/s41588-022-01272-z

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