Vectored antibody gene delivery mediates long-term contraception

Development of non-surgical methods of long-term or permanent contraception remains a challenge. Towards this objective, we show that intramuscular injection of a replication-incompetent, recombinant adeno-associated virus (rAAV) designed to express an antibody that binds gonadotropin-releasing hormone (GnRH), a master regulator of reproduction in vertebrates, results in long-term infertility in male and female mice. Female mice are also rendered infertile through rAAV-dependent expression of an antibody that binds to the zona pellucida (ZP), a glycoprotein matrix that surrounds the egg and functions as a sperm-binding site. Many proteins known or suspected to be important for reproduction can be targeted, potentially reversibly, using this approach, which we refer to as vectored contraception (VC).