# MitoPac female killing systems in mosquitoes

> **NIH AI R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2026 · $439,375

## Abstract

PROJECT SUMMARY
 Dengue, chikungunya, and Zika are diseases transmitted by Aedes aegypti. One strategy to reduce Ae.
aegypti populations is to release non-biting male mosquitoes that pass female killing genes to their progeny.
Over time and with many releases, this can lead to a significant suppression of the mosquito population,
decreasing transmission of the pathogens they vector. Some female-killing technologies are available for this
vector, but these technologies have some challenges that support the development of additional control
technologies. To address this need, we aim to build new tools to generate female-killing technologies in Ae.
aegypti. We focus on developing novel mitochondrial-targeted restriction endonucleases (mtREs) and CRISPR
systems to kill females with flexible designs and components amenable for future development in a wide
variety of mosquito vectors. As part of these efforts, we will explore switch-like cis-regulatory polycomb
response elements (PREs) to modulate the transcriptional activity of the mtREs and Cas9. In Aim 1, we will
selectively express the small mtRE, PacI, in female mosquitoes. Female-specific expression of PacI will be
achieved by driving PacI expression with a female-specific promoter or by encoding a female-specific intron of
the highly conserved doublesex (dsx) gene into the coding sequence of PacI. These expression systems will
be further optimized by integrating the PRE upstream of the PacI promoter. In Aim 2, we will also use PREs to
develop high precision heat shock-inducible and female-specific Cas9 expression systems. Heat shock
promoters can still have activity at low temperatures, and Cas9 often has high activity, which can interfere with
strain survival and the desired female-killing phenotype, so we aim to use PREs to minimize the issues. To
achieve female specificity, the heat shock Cas9 will be designed to target female-specific essential genes, or
the Cas9 will be engineered to encode a female-specific d

## Key facts

- **NIH application ID:** 11286058
- **Project number:** 1R21AI196522-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Omar Sultan Akbari
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $439,375
- **Award type:** 1
- **Project period:** 2026-02-19T00:00:00 → 2028-01-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11286058

## Citation

> US National Institutes of Health, RePORTER application 11286058, MitoPac female killing systems in mosquitoes (1R21AI196522-01). Retrieved via AI Analytics 2026-07-03 from https://api.ai-analytics.org/grant/nih/11286058. Licensed CC0.

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