Anopheline mosquitoes are the primary vectors of malaria, one of the deadliest and most costly diseases in human history. Measures to control malaria are becoming less effective as both insecticide- and drug-resistance increases. It is clear that new approaches are urgently needed. A new strategy to control mosquito-borne diseases proposes to introduce so-called effector genes or refractory genes into the mosquito that will render the mosquitoes ineffective vectors for pathogens. Developing the means to drive effector genes in natural populations is an urgent priority. The long term objective of this study is to develop an efficient and safe gene drive mechanism that will enable genetic strategies for the control of mosquito-borne infectious diseases. Recently, Chen and colleagues (2007) reported the creation of a synthetic genetic element called Medea in Drosophila that successfully drove population replacement in laboratory. The Drosophila Medea element consists of two parts, a maternally expressed toxin in the form of artificial microRNAs that suppress Myd88, an essential gene for early embryonic development, and a zygotic antidote in the form of a variant of Myd88 that lacks the microRNA targets thus insensitive to the toxin. Building on our preliminary results, we will test the hypothesis that a synthetic Medea gene drive system can be developed in Anopheles stephensi. We will 1) determine the transcriptome profiles during oogenesis and early embryogenesis in An. stephensi;2) select and test components of An. stephensi Medea;and 3) construct a complete An. stephensi Medea element and test for its maternal-effect selfish characteristics and gene drive ability.

Public Health Relevance

Anopheline mosquitoes are the primary vectors of malaria, which is one of the deadliest and most costly infectious diseases in human history. The long term objective of this study is to develop an efficient and safe gene drive mechanism that will enable genetic strategies for the control of mosquito-borne infectious diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI077680-04
Application #
8468629
Study Section
Special Emphasis Panel (ZRG1-VB-P (02))
Program Officer
Costero, Adriana
Project Start
2010-06-01
Project End
2015-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
4
Fiscal Year
2013
Total Cost
$355,542
Indirect Cost
$122,892
Name
Virginia Polytechnic Institute and State University
Department
Biochemistry
Type
Schools of Earth Sciences/Natur
DUNS #
003137015
City
Blacksburg
State
VA
Country
United States
Zip Code
24061
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