# Investigating oviductal gene editing delivered via extracellular vesicles as a novel contraceptive

> **NIH NIH K01** · COLORADO STATE UNIVERSITY · 2024 · $125,280

## Abstract

PROJECT SUMMARY/ABSTRACT
 This proposal describes a five-year mentored research career development project focused on evaluating
gene editing delivered via extracellular vesicles (EVs) as a novel approach for contraception. Almost half of
United States pregnancies are unintended, and available contraceptives often have undesirable side effects and
are effective only when utilized properly. Therefore, new easy-to-use contraceptive products with less side
effects are required. A survey of postpartum women indicated about 50% prefer permanent sterilization
compared with other contraceptives. The only permanent contraceptive available is surgical sterilization; while
routinely performed, there are anesthetic risks, high surgical cost, and requires facilities and personnel that are
absent in most low income locations. Non-surgical options for permanent contraception are currently unavailable.
 By secreting proteins that allow sperm capacitation, fertilization, and early embryo development, the
oviduct (fallopian tube) is essential for fertility. Oviductal epithelial cell progesterone receptor (PGR) and oviduct
specific glycoprotein (OVGP1) gene knockouts in mice induce infertility and reduce litter sizes, respectively.
Gene editing using CRISPR-cas9 has recently gained popularity in a clinical trial for sickle cell anemia and has
been used to edit neoplastic genes resulting in tumor shrinkage in rodent models in vivo. However, tissue-specific
targeting of CRISPR-cas9 ribonucleoproteins (RNPs) and in vivo transfection are challenging. EVs contain
proteins and nucleic acids within a lipid bilayer and are naturally secreted for intercellular communication.
Because EVs are produced in vivo for cell transport, they circumvent immune clearance, avoid hypersensitivity
reactions, and gain entry to cells that may not be accessible for foreign compounds alone. The overall goal of
this proposal is to evaluate the utility of EVs for targeting RNPs to oviductal cells. Specifically, we will evaluate
in vivo biodistribution of EVs deposited intrauterine in a mouse model to determine dissemination of EVs (Aim
1). Then, we will determine in vitro gene editing of EVs loaded with RNPs by designing guide RNAs to knock out
essential fertility genes (PGR, OVGP1) in oviductal organoids (Aim 2.1) prior to assessing in vivo gene editing
in a mouse model followed by a breeding trial to evaluate utility as a permanent contraceptive (Aim 2.2). In
addition to generating knowledge on mechanisms influencing oviductal function, this project will lead to
optimization of conditions for efficient delivery of CRISPR-cas9 RNPs to oviductal cells. Findings could lay the
foundation for development of a non-surgical, permanent contraception for women.
 The candidate is a postdoctoral fellow at Colorado State University and has assembled a diverse team
of experts to serve on her advisory committee. This proposal builds upon the candidate’s previous research
background and will augment her ex...

## Key facts

- **NIH application ID:** 10914937
- **Project number:** 5K01OD032455-02
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Riley Thompson-Brandhagen
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $125,280
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914937

## Citation

> US National Institutes of Health, RePORTER application 10914937, Investigating oviductal gene editing delivered via extracellular vesicles as a novel contraceptive (5K01OD032455-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10914937. Licensed CC0.

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