Efficient kidney gene transfer and proximal tubule transduction using self-complementary AAV.cc47 vectors

This is the authors' abstract. We don't add key points for this paper.

and in human kidney organoids compared to AAV9, mostly within the proximal tubule (PT) epithelium. We then developed a quantitative analysis method of transgene expression utilizing automated classification of nephron cell types coupled with cellular expression. Despite exhibiting similar biodistribution to AAV9 in renal and extrarenal tissues, AAV.cc47 consistently transduced the kidney at higher efficiency, with >80% of PT epithelium transduced at low, systemically administered vector dose. Self-complementary AAV.cc47 vectors appear to transduce a subset of PT epithelium, with undetectable transduction of non-PT cells. This method could be adapted to evaluate different AAV vectors transducing other kidney cell types. We also demonstrate the utility of dual AAV.cc47 vectors to increase genome payload capacity for kidney gene transfer. AAV.cc47 represents a promising vector for use as a research tool and possibly clinical application for kidney disease.