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A Comprehensive Atlas of AAV Tropism in the Mouse

Walkey et al., Molecular Therapy. 2025.

https://pubmed.ncbi.nlm.nih.gov/39863928

Over the past three decades, adeno-associated viruses (AAVs) have emerged as the leading viral vector for in vivo gene therapy. This study presents a comprehensive atlas of AAV tropism in male and female mice, evaluating 10 naturally occurring AAV serotypes across 22 tissues using systemic delivery. Researchers employed a fluorescent protein activation approach to visualize AAV transduction patterns and detected transduction of unexpected tissues, including in adrenal glands, testes, and ovaries. Biodistribution closely matched the fluorescent signal intensity. This publicly available data set provides valuable insights into AAV vector targeting and supports optimal serotype selection for basic research and preclinical gene therapy applications in murine models. Supported by ORIP (U42OD026645, U42OD035581, U42OD026635), NCI, NHLBI, NICHD, and NIDDK.

Metabolic Transitions Define Spermatogonial Stem Cell Maturation

Voigt et al., Human Reproduction. 2022.

https://www.doi.org/10.1093/humrep/deac157

The spermatogonial stem cell (SSC) is the basis of male fertility. One potential option to preserve fertility in patients treated with anti-cancer therapy is isolation and laboratory culture of the juvenile SSC pool with subsequent transplantation to restore spermatogenesis. However, efficient culture of undifferentiated spermatogonia, including SSCs, in mammals other than rodents remains challenging. Investigators reported that the metabolic phenotype of prepubertal human spermatogonia is distinct from that of adult spermatogonia and that SSC development is characterized by specific metabolic transitions from oxidative phosphorylation to anaerobic metabolism. Supported by ORIP (R01OD016575) and NICHD.

Postpubertal Spermatogonial Stem Cell Transplantation Restores Functional Sperm Production in Rhesus Monkeys Irradiated Before and After Puberty

Shetty et al., Andrology. 2021.

https://onlinelibrary.wiley.com/doi/10.1111/andr.13033

Cancer treatment of prepubertal patients impacts future fertility due to the abolition of spermatogonial stem cells (SSCs). Prepubertal rhesus monkeys (n=6) were unilaterally castrated, and the remaining testes irradiated twice to insure loss of SSCs; the animals were treated with a vehicle or GnRH antagonist for 8 weeks (n=3/treatment). The cryopreserved prepubertal testicular tissue was allergenically transplanted into the intact testes of the monkeys after puberty. Recovery of viable donor epididymal sperm was observed in half the monkeys. These results illustrate that sperm production can be restored in primates by transplantation of testicular cells from cryopreserved untreated prepubertal testes into seminiferous tubules of the remaining testes. Supported by ORIP (P51OD011092), NICHD, and NCI.