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Self-Eliminating Strategy To Control Gene Drive

Award Number: R01AI148787
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/25/2020
PERIOD OF PERFORMANCE END DATE: 01/31/2031

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Self-Eliminating Strategy To Control Gene Drive - The ability to deliver pathogen-resistance genes into mosquito populations has long been sought as a potential alternative for disrupting dengue or malaria transmission where funds and infrastructure are the limiting factors in effective mosquito control. While effective gene drive transgenes based on CRISPR/Cas9 have been developed for model organism Drosophila and for malaria mosquitoes, Aedes aegypti, the most medically important vector of dengue, yellow fever and chikungunya viruses, lags behind for reasons that remain largely unexplored and unknown. In this project, D. melanogaster and A. aegypti will be employed to evaluate novel hypotheses regarding how genome structure and DNA repair influence both homing gene drive and transgene removal based on single strand annealing. Following from previous work, multigeneration cage experiments will be performed on this transgene removal strategy in the context of an active gene drive in both flies and mosquitoes, followed by a wave of transgene removal (Aim 1). Next, the role of local microhomology, nuclease characterisics and DNA repair protein recruitment will be examined on both the rates of both homing gene drive and transgene removal in A. aegypti, where gene drive has lagged behind (Aim 2). Finally, the role of chromosomal position on both homing gene drive and transgene removal will be tested in the context of both synthetic targets and new haplolethal target genes (Aim 3). This innovative approach takes advantage of naturally occurring processes that are conserved throughout eukaryota to completely eliminate all transgenic sequences following potential field releases. Thus, it is anticipated that this project will have a substantial impact on National and International conversations concerning gene drive technology as a whole, and will raise expectations for what is possible in any future trial to generate pathogen-resistant mosquitoes.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $749,703 )
2026	2026	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Allergy and Infectious Diseases Research	001	6	2/9/2026	COMPETING CONTINUATION	$749,703
2026	2024	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Allergy and Infectious Diseases Research	000	5	1/30/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $749,703

Issue Date FY: 2024 ( Subtotal = $739,348 )
2024	2024	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Allergy and Infectious Diseases Research	000	5	5/8/2024	NON-COMPETING CONTINUATION	$739,348
														Subtotal = $739,348

Issue Date FY: 2023 ( Subtotal = $740,241 )
2023	2023	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Allergy and Infectious Diseases Research	000	4	5/23/2023	NON-COMPETING CONTINUATION	$740,241
														Subtotal = $740,241

Issue Date FY: 2022 ( Subtotal = $741,091 )
2022	2022	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Allergy and Infectious Diseases Research	000	3	5/20/2022	NON-COMPETING CONTINUATION	$741,091
														Subtotal = $741,091

Issue Date FY: 2021 ( Subtotal = $741,900 )
2021	2021	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Allergy and Infectious Diseases Research	000	2	5/4/2021	NON-COMPETING CONTINUATION	$741,900
														Subtotal = $741,900

Issue Date FY: 2020 ( Subtotal = $732,437 )
2020	2020	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Allergy and Infectious Diseases Research	000	1	6/25/2020	NEW	$732,437
														Subtotal = $732,437

Grand Total All Awards = $4,444,720

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Self-Eliminating Strategy To Control Gene Drive

Award Number: R01AI148787

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/25/2020

PERIOD OF PERFORMANCE END DATE: 01/31/2031

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