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Evaluation of a PPMO Inhibitor of Lassa Virus Infection and Disease in a Guinea Pig Model

Award Number: U3RAI156433
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Evaluation of a PPMO Inhibitor of Lassa Virus Infection and Disease in a Guinea Pig Model ABSTRACT: Lassa fever (LF) is caused by infection with Lassa virus (LASV), and is currently a major human disease problem in much of West Africa, causing thousands of deaths annually. Recent outbreaks of LF have been characterized by an increased number of cases and larger geographic footprint compared to previous outbreaks, and constitute a burgeoning public health crisis. In addition, the number of LF cases imported into non-endemic countries is growing, and there is also concern that LASV could be used as an agent of biological warfare. There is as yet no licensed vaccine or specific antiviral therapeutic to intervene against LASV-infections and treat patients with LF, and current treatment options have poor efficacy. There is therefore an immediate and critical medical need for new antiviral compounds to address LASV. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are a class of single-stranded-nucleic acid analogs that can enter cells readily and interfere with the production of viral proteins through steric blocking of complementary RNA. PPMO have shown considerable antiviral efficacy in vitro and in vivo against a number of RNA viruses, including several arenaviruses. We propose to synthesize two PPMO targeting highly conserved RNA sequences in the genomic termini of the LASV genome. Each PPMO will be tested in a non-cytotoxic dose-range for antiviral activity against several genetically- disparate strains of LASV. The PPMO exhibiting the highest antiviral efficacy in vitro will then be advanced to testing in a guinea pig model of LASV disease. Animal weight, temperature, appearance and behavior, along with mortality and viral titer in several tissues will be monitored. This study is designed to evaluate the ability of PPMO to reduce morbidity and mortality in a small-animal model of of severe LASV-disease. If successful, the project will produce an inhibitor that would be immediately useful as a research reagent against any strain of LASV and as a candidate for further development as a therapeutic agent against LASV infections in humans.


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: 2022 ( Subtotal = $74,250 )
2022	2022	OREGON STATE UNIVERSITY	1500 SW JEFFERSON ST	CORVALLIS	OR	97331	BENTON	USA	Allergy and Infectious Diseases Research	000	2	4/8/2022	NON-COMPETING CONTINUATION	$74,250
2022	2022	OREGON STATE UNIVERSITY	1500 SW JEFFERSON ST	CORVALLIS	OR	97331	BENTON	USA	Allergy and Infectious Diseases Research	002	2	4/11/2022	NON-COMPETING CONTINUATION	$0
2022	2021	OREGON STATE UNIVERSITY	1500 SW JEFFERSON ST	CORVALLIS	OR	97331	BENTON	USA	Allergy and Infectious Diseases Research	001	1	4/11/2022	NEW	$0
														Subtotal = $74,250

Issue Date FY: 2021 ( Subtotal = $74,250 )
2021	2021	OREGON STATE UNIVERSITY	1500 SW JEFFERSON ST	CORVALLIS	OR	97331	BENTON	USA	Allergy and Infectious Diseases Research	000	1	5/6/2021	NEW	$74,250
														Subtotal = $74,250

Grand Total All Awards = $148,500

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Evaluation of a PPMO Inhibitor of Lassa Virus Infection and Disease in a Guinea Pig Model

Award Number: U3RAI156433

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

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