Research HighlightPublished: 26 February 2025Gene therapyMonica Wang1 Nature Reviews Nephrology (2025)Cite this articleMetrics detailsSubjectsDisease geneticsGene therapyKidney diseasesMolecularly targeted therapyEffective gene delivery to the kidneys is complicated by the intricacies of kidney anatomy and physiology, and cross-species differences create further barriers in the translation of preclinical research. A study by Aravind Asokan and colleagues now demonstrates the potential of adeno-associated virus (AAV) library evolution for the development of human kidney gene therapies.Delivery of AAV.k13 and AAV.k20 intravenously in mice not only led to higher mCherry expression compared with the parental AAV9 variant, but was also effective for the delivery of a programmed death ligand 1 (PD-L1) transgene, with evidence of robust PD-L1 expression in the kidneys after 4 weeks. In pig kidney grafts, retrograde ureteral delivery of mCherry packaged in the new AAV variants resulted in broad protein expression throughout the proximal tubules, with lower levels in the distal tubules, following transplantation into the same animal. Despite no differences in viral biodistribution, kidney expression levels of mCherry mRNA were significantly higher when the transgene was packaged in the new AAV variants compared with the parental AAV9 capsid.This is a preview of subscription content, access via your institutionAccess optionsAccess Nature and 54 other Nature Portfolio journalsGet Nature+, our best-value online-access subscription24,99 € / 30 dayscancel any timeLearn moreSubscribe to this journalReceive 12 print issues and online access209,00 € per yearonly 17,42 € per issueLearn moreBuy this articlePurchase on SpringerLinkInstant access to full article PDFBuy nowPrices may be subject to local taxes which are calculated during checkoutReferencesOriginal articleRosales, A. et al. Evolving adeno-associated viruses for gene transfer to the kidney via cross-species cycling of capsid libraries. Nat. Biomed. Eng. https://doi.org/10.1038/s41551-024-01341-0 (2025)Article PubMed Google Scholar Download referencesAuthor informationAuthors and AffiliationsNature Reviews Nephrology http://www.nature.com/nrnephMonica WangAuthorsMonica WangView author publicationsYou can also search for this author in PubMed Google ScholarCorresponding authorCorrespondence to Monica Wang.Rights and permissionsReprints and permissionsAbout this article