Several years ago we pioneered a new approach to long term contraception, vectored contraception VC LI ET AL , 2015 we used a gene therapy vector a non replicating adenoassociated virus, AAV to…

The California Institute of Technology (Caltech) was awarded a $552,904 cooperative agreement by the Bureau of Land Management (BLM) National Office through the Wild Horse and Burro Resource Management program (CFDA 15.229) to develop a gene therapy-based contraceptive for wild horses. The two-year project beginning January 1, 2023 aims to test the hypothesis that long-term infertility can be achieved through low-dose expression of an engineered protein binding tightly to Juno, a protein essential for sperm binding and fertilization in mammals. In year one, Caltech will conduct proof-of-principle experiments in mice using Juno-binding proteins under development at the laboratory of David Baker to saturate sperm-binding sites over time and prevent fertilization. Pending identification of additional partners, year two will produce a product for subsequent testing in horses to support BLM's mission of managing wild horse populations on public lands.

Several years ago we pioneered a new approach to long term contraception, vectored contraception VC LI ET AL , 2015 we used a gene therapy vector a non replicating adenoassociated virus, AAV to package and deliver into mouse muscle through an IM injection a gene encoding either an antibody that binds gnrh or a component of the zona pellucida expression of these antibodies resulted in long term infertility in males and females, and females, respectively gene therapy based approaches to contraception are attractive because use of a cloned gene ensures that all animals experience a similar response, unlike what often happens with vaccines also, work in other large animals such as dogs, non human primates and humans show that AAV is stable in post mitotic cells such as muscle and can express at high levels for many years the challenge to extending this approach to equids relates to dose how can we produce enough protein to inhibit a process essential for fertility, cheaply, in animals ten thousand times larger than a mouse mice have 5 MLS of blood, horses 50 liters the hypothesis we will test is that long term infertility can be achieved at low dose through AAV based expression of an engineered protein that binds very tightly to a specific region of juno, a protein expressed on oocytes whose function is essential for sperm binding and fertilization in mammals the specific hypothesis to be tested is that a modest number of AAV genomes, and the low circulating levels of a high affinity juno binding protein that ensue, will over time saturate all the sperm binding sites on juno, preventing fertilization our goals in this 2 year proposal are 1 to do proof of principle experiments that will test this idea in the mouse using juno binding proteins under development by david baker s lab see letter of support and 2 to produce a product to be subsequently tested in the horse, pending the identification of funded collaborators or a new call for proposals in subsequent years