title: Vectored antibody gene delivery mediates long-term contraception.
abstract: 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).
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Alejandra I
authors.initials: AI
authors.lastname: Olvera
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Omar S
authors.initials: OS
authors.lastname: Akbari
authors.affiliation: Beckman Institute Proteome Exploration Laboratory, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Annie
authors.initials: A
authors.lastname: Moradian
authors.affiliation: Beckman Institute Proteome Exploration Laboratory, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sweredoski
authors.affiliation: Beckman Institute Proteome Exploration Laboratory, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Sonja
authors.initials: S
authors.lastname: Hess
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: haybruce@caltech.edu.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Hay
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000378:metabolism*; D003267:Contraception / Q000379:methods*; D000229:Dependovirus / Q000235:genetics; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007273:Injections, Intramuscular; D008297:Male; D051379:Mice; D015044:Zona Pellucida / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D007987:Gonadotropin-Releasing Hormone