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Error-corrected next-generation sequencing to advance nonclinical genotoxicity and carcinogenicity testing

Error-corrected next-generation sequencing (ecNGS) is an emerging technology with the potential to revolutionize the field of genetic toxicology. Here, we present recommendations from an expert working group convened to discuss potential applications, advantages and challenges associated with implementing ecNGS in nonclinical safety studies.
  1. Francesco Marchetti

    1. Health Canada, Ottawa, Ontario, Canada.

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  2. Renato Cardoso

    1. MilliporeSigma, Rockville, MD, USA.

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  3. Connie L. Chen

    1. Health and Environmental Sciences Institute, Washington, DC, USA.

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  4. George R. Douglas

    1. Health Canada, Ottawa, Ontario, Canada.

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  5. Joanne Elloway

    1. Safety Sciences, Clinical Pharmacology & Safety Sciences R&D, AstraZeneca, Cambridge, UK.

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  6. Patricia A. Escobar

    1. Merck & Co., Rahway, NJ, USA.

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  7. Tod Harper Jr

    1. Amgen, Thousand Oaks, CA, USA.

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  8. Robert H. Heflich

    1. US Food and Drug Administration, National Center for Toxicological Research, Jefferson, AR, USA.

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  9. Darren Kidd

    1. Labcorp Early Development Laboratories Limited, Harrogate, UK.

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  10. Anthony M. Lynch

    1. GlaxoSmithKline, Stevenage, UK.

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  11. Meagan B. Myers

    1. US Food and Drug Administration, National Center for Toxicological Research, Jefferson, AR, USA.

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  12. Barbara L. Parsons

    1. US Food and Drug Administration, National Center for Toxicological Research, Jefferson, AR, USA.

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  13. Jesse J. Salk

    1. TwinStrand Biosciences., Seattle, WA, USA.

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  14. Raja S. Settivari

    1. Corteva Agriscience, Newark, DE, USA.

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  15. Stephanie L. Smith-Roe

    1. National Institute of Environmental Health Sciences, Division of Translational Toxicology, Research Triangle Park, NC, USA.

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  16. Kristine L. Witt

    1. National Institute of Environmental Health Sciences, Division of Translational Toxicology, Research Triangle Park, NC, USA.

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  17. Carole Yauk

    1. University of Ottawa, Ottawa, Ontario, Canada.

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  18. Robert R. Young

    1. MilliporeSigma, Rockville, MD, USA. Current: Consultant, Bethesda, MD, USA.

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  19. Shaofei Zhang

    1. Pfizer, Groton, CT, USA.

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  20. Sheroy Minocherhomji

    1. Amgen, Thousand Oaks, CA, USA. Current: Eli Lilly and Company, Indianapolis, IN, USA.

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Carcinogenicity assessment is a major focus in regulatory safety testing. Mutagenesis is a hallmark of cancer, a key feature of carcinogens, and it underlies many non-cancer-related heritable human diseases1. Thus, assessing the potential of a new xenobiotic, such as an investigational drug, for its ability to cause mutations or genomic instability is critical for human and environmental health risk assessment.

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Nature Reviews Drug Discovery 22, 165-166 (2023)

doi: https://doi.org/10.1038/d41573-023-00014-y

Acknowledgements

We thank the Health and Environmental Sciences Institute (HESI) of the Genetic Toxicology Technical Committee (GTTC) members for their scientific input. All authors are members of the HESI GTTC. This article reflects the views of the authors and does not necessarily reflect the official views or policy of the US Food and Drug Administration, the National Institutes of Health, or the US government.

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Competing Interests

J.J.S. is an employee and equity holder at TwinStrand Biosciences Inc., and is an author on one or more duplex sequencing-related patents. R.C., J.E., P.A.E., T.H. Jr, D.K., A.M.L., J.J.S., S.Z. and S.M. are employed by companies that may be engaged in using error-corrected sequencing.

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