# Synthetic mRNA-mediated reversible immunocontraception

> **NIH NIH R33** · EMORY UNIVERSITY · 2023 · $663,083

## Abstract

Project summary
Currently 72% of women who practice contraception use hormonal methods, but there is frequent dissatisfaction
with these methods, due to quality of life and safety concerns. Therefore, there is a clear need for new
approaches to non-hormonal female contraceptives that are easy to use, woman-applied, and have a
controllable duration of action. Reversible immunocontraception offers a non-hormonal solution, where anti-
sperm antibodies are introduced into the female reproductive tract (FRT) and inhibit sperm function. This
approach, though, has a number of challenges including: discovery of a specific and effective monoclonal
antibody (mAb) against a human sperm antigen, and a safe and reliable method for introduction of mAbs that is
temporally and spatially controllable. For this grant application, reproductive biology expertise and a molecular
toolbox has been brought together to overcome these challenges. An anti-sperm antibody has been identified
with well-characterized mechanisms of action that impact fertility, and an innovative method has been identified
to deliver the antibody to the FRT. Here a synthetic mRNA-based approach is proposed to deliver a sperm
agglutinating and mucus trapping antibody to the FRT. To date, the ability to express high levels of antibody for
over 28 days with a single administration of mRNA in the FRT of sheep has been demonstrated. Delivery is
achieved through direct, rapid, aerosol exposure of the FRT epithelium to naked mRNA in water. Persistence
of the antibody in secretions was achieved through the incorporation of a GPI-linker into the heavy chain of the
antibody. This combination allows for rapid delivery and expression, and for controllable persistence of the
protective mAb in secretions. In the R61 phase, the mechanism of delivery under relevant conditions will be
optimized and explored; antibody design questions will also be addressed that will allow for tunable persistence
of the antibody in mucus secretions. In the R33 phase, pharmacokinetic experiments will be performed in
macaques, as well as continued antibody optimization. Last, sperm challenge experiments will be performed in
vivo to demonstrate efficacy. The long-term goal is to develop a cost-effective mRNA-based approach for
expressing anti-sperm antibodies in the FRT. The short-term goals are to optimize the approach, answer
mechanistic questions, and demonstrate pre-clinical feasibility in the macaque model. If successful, a new
paradigm for contraception will be demonstrated, one that can be combined with the co-expression of anti-STI
antibodies, such as those against HIV and HSV-2.

## Key facts

- **NIH application ID:** 10695023
- **Project number:** 5R33HD099745-05
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Deborah J Anderson
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $663,083
- **Award type:** 5
- **Project period:** 2019-09-13 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10695023

## Citation

> US National Institutes of Health, RePORTER application 10695023, Synthetic mRNA-mediated reversible immunocontraception (5R33HD099745-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10695023. Licensed CC0.

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