CRISPR Improves ex vivo Donor Organ Treatment

Organ transplantation is limited not only by donor shortages but also by the high number of organs discarded because of concerns over quality or latent viral infection. The authors describe how CRISPR-Cas systems could be delivered during normothermic machine perfusion, a procedure that maintains donor organs outside the body while providing an opportunity to modify their biology before implantation. Rather than permanent genome editing, their approach uses a ψDNA-guided Cas12a platform to achieve programmable RNA knockdown, aiming to transiently suppress injury-response pathways or reduce viral RNA in donor tissue.

The article includes early proof-of-concept findings from the authors’ own programme, reporting substantial target RNA knockdown in ex vivo human kidney biopsy samples after optimisation of perfusion conditions. However, the authors emphasise that translating this to whole-organ treatment will require overcoming challenges related to tissue penetration, donor-to-donor variability, persistence of RNA silencing after transplantation, off-target assessment and scalable GMP manufacturing.

They also discuss how ex vivo organ treatment presents distinct regulatory and clinical considerations compared with existing ex vivo CRISPR cell therapies, while potentially fitting within established transplant workflows if organ-scale efficacy can be demonstrated. Rather than presenting a completed experimental study, the article provides a translational roadmap for developing CRISPR-based therapies during donor organ perfusion and highlights the technical hurdles that remain before clinical implementation.

The article was led by Santosh Rananaware, Rushi Shah and Piyush Jain, who are co-founders of CasNx, Florida, USA. It was published in Nature Reviews Bioengineering on 29 June 2026.