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mRNA-encoded Cas13 as a pan-respiratory antiviral

Award Number: R01AI175428
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: 01/23/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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mRNA-encoded Cas13 as a pan-respiratory antiviral - Project Summary There are over 200 viruses known to infect humans and they contribute to 6.6% of global mortality. We have approximately 91 drugs for 10 viral species and vaccines for only 16. Reassortment and antigenic changes pose challenges to vaccine efficacy; this has clearly been demonstrated during the COVID pandemic. Current drug development is focused on small molecules and neutralizing antibodies, which require high doses or frequent re-dosing to obtain functional outcomes and have also been challenged by antigenic changes. Thus, it is crucial to address the need for higher efficiency and broader spectrum antivirals. To address this need we are proposing an entirely different paradigm for antiviral development, an mRNA-encoded activatable RNase, Cas13, as a platform for a pan-respiratory treatment. Cas13 represents a programmable RNase that can directly target and degrade multiple viral messenger or genomic RNA. Synthetic mRNA is being used to deliver the RNase, as it allows for transient, non-viral delivery, with an improved safety profile over other gene therapy vectors1. Given achieving pan-respiratory results with a single mRNA-encoded Cas13 based drug is not trivial, critical steps towards that goal can be achieved by focusing on the three most impactful respiratory viruses in circulation, RSV, influenza and SARS-CoV-2. To date, our team was the first to demonstrate efficacy of mRNA-encoded Cas13 in vitro and in vivo via nebulizer-based lung delivery against influenza in the mouse model and SARS- CoV-2 in the hamster model in our recent publication in Nature Biotechnology. In order to achieve one drug for RSV, influenza and SARS-CoV-2 there are important questions/challenges that will need to be met. Thus, we will determine the optimal Cas13 species for multiple respiratory pathogens and investigate the mechanism of action of Cas13 for each virus. We will also demonstrate single drug efficacy against RSV, influenza and SAR- CoV-2 in vivo in mouse and hamster models, given as treatments for the individual viral infections, during co- infection (influenza and SAR-CoV-2), and to mitigate transmission of SARS-CoV-2.


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 = $709,376 )
2026	2026	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	4	1/14/2026	NON-COMPETING CONTINUATION	$709,376
														Subtotal = $709,376

Issue Date FY: 2025 ( Subtotal = $688,094 )
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	3	12/16/2024	NON-COMPETING CONTINUATION	$688,094
														Subtotal = $688,094

Issue Date FY: 2024 ( Subtotal = $709,376 )
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	2	12/26/2023	NON-COMPETING CONTINUATION	$638,439
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	2	5/21/2024	NON-COMPETING CONTINUATION	$70,937
														Subtotal = $709,376

Issue Date FY: 2023 ( Subtotal = $723,501 )
2023	2023	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	001	1	4/6/2023	NEW	$0
2023	2023	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	1	1/23/2023	NEW	$723,501
														Subtotal = $723,501

Grand Total All Awards = $2,830,347

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mRNA-encoded Cas13 as a pan-respiratory antiviral

Award Number: R01AI175428

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: 01/23/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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