Evolving adeno-associated viruses for gene transfer to the kidney via cross-species cycling of capsid libraries.

ABSTRACT: The difficulty of delivering genes to the kidney has limited the translation of genetic medicines, particularly for the more than 10% of the global population with chronic kidney disease. Here we show that new variants of adeno-associated viruses (AAVs) displaying robust and widespread transduction in the kidneys of mice, pigs and non-human-primates can be obtained by evolving capsid libraries via cross-species cycling in different kidney models. Specifically, the new variants, AAV.k13 and AAV.k20, were enriched from the libraries following sequential intravenous cycling through mouse and pig kidneys, ex vivo cycling in human organoid cultures, and ex vivo machine perfusion in isolated kidneys from rhesus macaques. The two variants transduced murine kidneys following intravenous administra

SUBMITTER: Rosales A 

PROVIDER: S-EPMC12261118 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature