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Extracellular vesicles encapsulating CRISPR machinery for treatment of SARS-CoV-2 infection

Award Number: R21AI171944
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: 01/19/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Extracellular vesicles encapsulating CRISPR machinery for treatment of SARS-CoV-2 infection - Summary/Abstract SARS-CoV-2 has caused the deaths of millions of people globally. Effective antiviral therapeutic treatment options are urgently needed. CRISPR-mediated genome editing has provided a very promising avenue for treatment of a variety of genetic diseases. Particularly, the CRISPR-Cas13 system has been demonstrated to possess the potential of inhibiting SARS-CoV-2 and influenza infections by degradation of viral genomic RNA and viral mRNA. However, it is still very challenging to deliver the CRISPR machinery to initiate genome editing efficiently in vivo. Extracellular vesicles (EVs) contain a variety of molecular components including lipids, mRNA, microRNAs, and proteins. A large body of studies has shown that EVs mediate cell-to-cell communication by transmitting their encapsulated contents. This proposal intends to construct EVs encapsulating the CRISPR machinery and deliver the EVs to respiratory epithelial cells to inhibit SARS-CoV-2 proliferation in vivo. We will therefore genetically engineer the Cas13d protein so that Cas13d/CRISPR-RNA (crRNA) ribonucleoprotein complex can be encapsulated into EVs. We will also engineer the membrane of EVs, such that EVs target respiratory epithelial cells and deliver Cas13d/crRNA for inhibiting SARS-CoV-2 viral assembly and proliferation, thereby inhibiting COVID-19. This study will allow us to understand the feasibility of an EVs-based vehicle to deliver genome editing machinery to inhibit SARS-CoV-2 proliferation in lung epithelial cells. This study will provide a treatment option for COVID-19 patients to reduce disease severity and mortality.


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 = $0 )
2026	2024	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	2	12/1/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	2	11/14/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $184,222 )
2024	2024	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	2	12/5/2023	NON-COMPETING CONTINUATION	$165,800
2024	2024	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	001	2	5/17/2024	NON-COMPETING CONTINUATION	$18,422
														Subtotal = $184,222

Issue Date FY: 2023 ( Subtotal = $221,972 )
2023	2023	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	1	1/19/2023	NEW	$221,972
														Subtotal = $221,972

Grand Total All Awards = $406,194

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Extracellular vesicles encapsulating CRISPR machinery for treatment of SARS-CoV-2 infection

Award Number: R21AI171944

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: 01/19/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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