Recent developments in gene-therapy vector technologies make it possible for rapid design, production, and analysis of complex genetic mouse models, that circumvent traditional breeding, genotyping and maintenance of multiple complex mouse lines. We have characterised multiple technologies to define approaches to selectively deliver genetic constructs to different somatic cell populations of the testis. Using these, we are able to perturb, inhibit, induce, label, track or replace gene function for multiple genes simultaneously in wild-type mice, with analysis possible as little as 48 hours post-treatment.
Our results demonstrate differing applications for alternative vector systems, including for generic and bespoke Lentivirus, adenovirus, adeno-associated virus, and nanoparticles, with or without cell-selective targeting.
Using a combination of these systems, in single treatments we are able to selectively block spermatogenesis (for more than 1 year) or restore spermatogenesis in mutant animals. Or alternatively, selectively inhibit or enhance steroid hormone production by the testis.
Together these approaches provide proof of principle for future methodologies to selectively manipulate testis function in support of, or to suppress, spermatogenesis, and to support lifelong male health through manipulation of androgen production and action.