# Gene delivery for Anopheles mosquitoes

> **NIH NIH R01** · PENNSYLVANIA STATE UNIVERSITY, THE · 2020 · $381,150

## Abstract

Project Summary
Human malaria, responsible for inordinate mortality, morbidity and economic loss worldwide, is caused by
protozoan parasites in the genus Plasmodium that are obligatorily transmitted by Anopheles mosquitoes.
Failure of traditional control methodologies has stimulated efforts to develop novel strategies to control the
mosquito vectors of malaria, particularly An. gambiae. While transgenic manipulation of Anopheles species
has been accomplished, routine manipulation of An. gambiae has proven challenging, and the technology to do
so is not broadly available among non-specialized laboratories. The development of novel, easy to use tools for
routine forward genetics in An. gambiae is critical for both applied strategies for malaria control and basic
research into the genetics and host/parasite interactions of this important mosquito vector species.
Densonucleosis viruses, or “densoviruses” (DNVs), are single-stranded DNA viruses in the family Parvoviridae
with very small genomes (4-6 kb) that are flanked by terminal hairpin structures at the 5-prime and 3-prime
ends. The entire viral genome can be placed into an infectious plasmid from which functional virus will be
produced upon transfection into an appropriate cell line. In our laboratory, we have identified only known
densovirus (AgDNV) capable of infection and dissemination in Anopheles gambiae. AgDNV replicates
preferentially in adult mosquito tissues to very high titer, but is completely non-pathogenic. We have developed
and validated novel techniques to use AgDNV to express secreted effectors or microRNAs that can modulate or
alter patterns of Anopheles gene expression. Our overall hypothesis is that AgDNV can be used overexpress or
knock down expression of specific genes of interest in Anopheles gambiae, leading to phenotypes of basic and
applied importance. This overall hypothesis will be addressed in the following specific aims: 1) Develop an
AgDNV-based gene transduction system for routine forward genetics in An. gambiae, focusing on modulation
of Plasmodium falciparum infection/transmission; 2) Develop an AgDNV-based system for routine reverse
genetics in Anopheles gambiae, focusing on modulation of P. falciparum infection/transmission and mosquito
fitness; 3) Characterize and quantify AgDNV infection of the male mosquito reproductive system, and
determine the potential for using auto-dissemination to introduce AgDNV into mosquito cage populations.
This research will result in the development of a novel toolset for addressing basic questions in Anopheles and
Plasmodium biology, as well as the development of potential control agents for human malaria.

## Key facts

- **NIH application ID:** 9900713
- **Project number:** 5R01AI128201-04
- **Recipient organization:** PENNSYLVANIA STATE UNIVERSITY, THE
- **Principal Investigator:** Jason L Rasgon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,150
- **Award type:** 5
- **Project period:** 2017-05-10 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900713

## Citation

> US National Institutes of Health, RePORTER application 9900713, Gene delivery for Anopheles mosquitoes (5R01AI128201-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9900713. Licensed CC0.

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