Genetic Discovery and In Vivo Validation of Contraceptive Targets by AAVs

Viviana Gradinaru of the California Institute of Technology in the U.S. will perform imaging-based, high-throughput screens using adeno-associated virus (AAV) delivery vectors to rapidly identify ovary-specific macromolecules that are essential for fertility and could be used to develop non-hormonal contraceptives. They will compile a comprehensive list of candidate ovary-specific macromolecules, including RNAs and micropeptides, by applying machine learning algorithms and structural analyses to existing datasets and also perform Riboseq on mouse and human ovarian tissues to identify all the proteins being translated. They will then test these candidates by developing an oocyte and follicle cell-based loss-of-function screening platform using AAV to safely, efficiently, and specifically deliver the macromolecule-targeting constructs to the cells. The most promising AAV-based candidates will then be tested directly in mouse follicle cultures and then in vivo to identify those that are critical for female fertility and have reversible effects.