# CRISPR/Cas9 and small molecules for targeting sperm function and fertilization

> **NIH NIH P01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $158,288

## Abstract

PROJECT 2 SUMMARY (CRISPR/Cas9 and small molecules for targeting sperm function and fertilization)
The overall goals of Project 2 are to use CRISPR/Cas9 to understand the formation of functional sperm
and identify small-molecule probes and preclinical candidates to target fertilization-required proteins
for a contraceptive effect in vivo. Population growth is a major worldwide issue, and our resources cannot
continue to sustain these population increases, and because of this, NICHD has made contraception a priority
focus area. Because our group is focused on the development of contraceptives that specifically target sperm
and fertilization, these germ cell-selective contraceptives would eliminate unwanted side effects. The Ikawa
laboratory has developed the CRISPR/Cas9 system to efficiently mutate genes in vivo including the Cetn1 and
Prm1 genes required for male fertility. In this P01, we will use CRISPR/Cas9 technology to advance our
understanding of fertility pathways in all three Projects and generate useful information to move these target
proteins and other related pathway proteins into the DEC-Tec Core for screening. For contraceptive targets in
Project 2, we will focus on two sperm-egg fusion transmembrane/signaling proteins and four sperm motility-
related proteins that we have shown are evolutionarily-conserved and required only for male fertility. The Ikawa
laboratory has effectively used the CRISPR/Cas9 system to generate mutations in over 200 mouse genes
including the genes described in this proposal. This strategy has also successfully produced knockin of tag
sequences into loci. We have used CRISPR/Cas9 independently and in collaboration with the Matzuk
laboratory (Project 1) to uncover proteins required for sperm-egg fusion and sperm motility. Functional analysis
of these mouse models will help not only to decipher the mechanisms by which these proteins function in
sperm-egg fusion and sperm motility but also to develop contraceptive drugs to target these essential
pathways. The screening of small molecules using the DEC-TEC Core will accelerate this process. Our overall
hypothesis is that CRISPR/Cas9 and DEC-Tec will help us to understand the network of interactions of these
proteins for sperm function, rapidly identify multiple small molecules that are directed at these essential
spermatogenic proteins, and create an assortment of contraceptives for men and women. The Specific Aims of
Project 2 are: 1) Manipulate the mouse genome and characterize the interrelationship of sperm-egg fusion
proteins; 2) Use CRISPR/Cas9 to study the mechanism of action of novel testis-specific proteins; and 3) Use
DEC-Tec to identify small-molecule drug-like probes and preclinical candidates to inhibit sperm motility-specific
and fertilization-specific proteins for a contraceptive effect in vivo. The success of Project 2 and this P01 grant
relies on the continued collaborations of Project 2 with Dr. Matzuk in Project 1, Drs. Sonnenburg, Lamb, and
Hu...

## Key facts

- **NIH application ID:** 10164828
- **Project number:** 5P01HD087157-05
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** MASAHITO IKAWA
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $158,288
- **Award type:** 5
- **Project period:** 2017-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10164828

## Citation

> US National Institutes of Health, RePORTER application 10164828, CRISPR/Cas9 and small molecules for targeting sperm function and fertilization (5P01HD087157-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10164828. Licensed CC0.

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