Down to BusinessPublished: 29 June 2026Santosh R. Rananaware ORCID: orcid.org/0000-0001-8789-57991,Karthik V. Narisetty1,Rushi A. Shah1,2 &…Piyush K. Jain1,3,4,5 Nature Reviews Bioengineering (2026) Cite this articleSave articleView saved researchSubjectsGene therapyNucleic-acid therapeuticsDonor organs are frequently discarded because of concerns about quality or pathogen risk, challenges that could be mitigated through ex vivo gene editing or silencing during machine perfusion. Here, we discuss the development of CRISPR-based approaches for ex vivo gene silencing in human donor organs, from proof of concept in kidney biopsies to the challenges of organ-scale translation.This is a preview of subscription content, access via your institutionAccess optionsSubscribe to this journalReceive 12 digital issues and online access to articles118,99 € per yearonly 9,92 € per issueLearn moreBuy this articlePurchase on SpringerLinkInstant access to the full article PDF.39,95 €Prices may be subject to local taxes which are calculated during checkoutFig. 1: Ex vivo gene silencing in donor organs using CRISPR–Cas during machine perfusion.ReferencesLi, X., Ding, R. & Cai, J. Organ transplantation: current status, challenges, and future prospects. MedComm 7, e70567 (2026).Article Google Scholar Mohan, S. et al. Factors leading to the discard of deceased donor kidneys in the United States. Kidney Int. 94, 187–198 (2018).Article Google Scholar Nasralla, D. et al. 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Rananaware, Karthik V. Narisetty, Rushi A. Shah & Piyush K. JainDepartment of Surgery, Division of Transplantation, University of Florida College of Medicine, Gainesville, FL, USARushi A. ShahDepartment of Chemical Engineering, University of Florida, Gainesville, FL, USAPiyush K. JainDepartment of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USAPiyush K. JainUF Health Cancer Center, University of Florida, Gainesville, FL, USAPiyush K. JainAuthorsSantosh R. RananawareView author publicationsSearch author on:PubMed Google ScholarKarthik V. NarisettyView author publicationsSearch author on:PubMed Google ScholarRushi A. ShahView author publicationsSearch author on:PubMed Google ScholarPiyush K. JainView author publicationsSearch author on:PubMed Google ScholarCorresponding authorsCorrespondence to Rushi A. Shah or Piyush K. Jain.Ethics declarationsCompeting interestsS.R.R., R.A.S. and P.K.J. are co-founders of CasNx, which is developing CRISPR-based technologies for ex vivo organ treatment and diagnostics. P.K.J. and S.R.R. are named inventors on patents related to ψDNA-guided CRISPR–Cas. P.K.J., S.R.R. and R.A.S. are named inventors on a provisional patent related to organ modification on perfusion pump filed through CasNx. CasNx has successfully secured an option agreement (UFAA21433) to license the University of Florida’s foundational DNA-guided CRISPR–Cas technology for improving organs prior to transplantation.Additional informationRelated linksCASGEVY: https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-diseaseRights and permissionsReprints and permissionsAbout this article