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Targeted delivery of genome editors in vivo

Nature Biotechnology volume 44, pages 49–59 (2026)Cite this article

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Abstract

Genome editing has revolutionized the treatment of genetic diseases, yet the difficulty of tissue-specific delivery currently limits applications of editing technology. In this Review, we discuss preclinical and clinical advances in delivering genome editors with both established and emerging delivery mechanisms. Targeted delivery promises to considerably expand the therapeutic applicability of genome editing, moving closer to the ideal of a precise ‘magic bullet’ that safely and effectively treats diverse genetic disorders.

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Fig. 1: Controlling delivery by route of administration.
Fig. 2: Controlling physical location of enzymes through molecular targeting.
Fig. 3: Controlling where genome editors are expressed.
Fig. 4: Controlling where genome editors have a phenotypic effect.
Fig. 5: Controlling in vivo delivery of therapeutic genome editors at multiple stages.

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Acknowledgements

We thank all members of the Doudna laboratory for their thoughtful input on the manuscript, especially K. Chen, J. Zeng and Z.W. Xue. The manuscript was funded by the following sources: Gladstone Institutes (J.A.D.), the HHMI (J.A.D.), National Heart, Lung, and Blood Institute grant 1R21HL173710-01 (J.A.D.) and Lawrence Livermore National Labs PROTECT grant, DE-AC52-07NA27344 (J.A.D.). J.A.D. also receives support from NIH/NIAID (U54AI170792, U19AI135990, UH3AI150552 and U01AI142817), NIH/NINDS (U19NS132303), NSF (2334028), DOE (DE-AC02-05CH11231, 2553571 and B656358), Apple Tree Partners (24180), UCB-Hampton University Summer Program, Mr. Li Ka Shing, Koret-Berkeley-TAU, Emerson Collective and the Innovative Genomics Institute (IGI). J.L.Y.W. was also funded by the Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship. We also acknowledge financial support from the James B. Pendleton Charitable Trust.

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Authors and Affiliations

  1. Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA

    Wayne Ngo, Jamie L. Y. Wu, Kevin M. Wasko & Jennifer A. Doudna

  2. Gladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA

    Wayne Ngo, Jamie L. Y. Wu & Jennifer A. Doudna

  3. California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA, USA

    Wayne Ngo, Jamie L. Y. Wu & Jennifer A. Doudna

  4. Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA

    Kevin M. Wasko & Jennifer A. Doudna

  5. Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA

    Jennifer A. Doudna

  6. Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

    Jennifer A. Doudna

  7. Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA

    Jennifer A. Doudna

  8. Li Ka Shing Center for Genomic Engineering, University of California, Berkeley, Berkeley, CA, USA

    Jennifer A. Doudna

  9. Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA

    Jennifer A. Doudna

Authors
  1. Wayne Ngo
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  2. Jamie L. Y. Wu
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  3. Kevin M. Wasko
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  4. Jennifer A. Doudna
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Contributions

Conceptualization: W.N., K.M.W. and J.A.D. Funding acquisition: J.A.D. Project administration: W.N. and J.A.D. Writing and editing: W.N., K.M.W., J.L.Y.W. and J.A.D.

Corresponding author

Correspondence to Jennifer A. Doudna.

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Competing interests

The Regents of the University of California have patents issued and/or pending for CRISPR technologies (on which J.A.D. is an inventor) and delivery technologies (on which J.A.D. and W.N. are co-inventors). J.A.D. is a cofounder of Azalea Therapeutics, Caribou Biosciences, Editas Medicine, Evercrisp, Scribe Therapeutics and Mammoth Biosciences. J.A.D. is a scientific advisory board member at Isomorphic Labs, BEVC Management, Evercrisp, Caribou Biosciences, Scribe Therapeutics, Mammoth Biosciences, The Column Group and Inari. She is also an advisor for Aditum Bio. J.A.D. is chief science advisor to Sixth Street, is a director at Johnson & Johnson, Altos and Tempus, and has a research project sponsored by Apple Tree Partners. All other authors declare no competing interests.

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Ngo, W., Wu, J.L.Y., Wasko, K.M. et al. Targeted delivery of genome editors in vivo. Nat Biotechnol 44, 49–59 (2026). https://doi.org/10.1038/s41587-025-02945-w

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