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Evaluation of Toxicity Score and Precise Snake Venom Analytics for Next Generation Antivenom Development

Award Number: SC2GM136606
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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ABSTRACT The overall goal of this project is to engage undergraduate and graduate students in innovative studies in molecular toxinology that have the potential to contribute to important advances in our understanding of snake venom pathology and the development of novel antibody-based therapeutics. According to WHO statistics, it is estimated that in 2020 there will be 125,000 new deaths world-wide reported due to snake envenomation. In spite of its importance for snake bite envenomation as a neglected tropical disease and global health issue, very little is known of the mechanism of action of snake venom and intrinsic toxic/lethal contribution. The scientific foundation for our study is that a specific combination of snake venom toxins plays a critical role in snakebites by causing necrosis, coagulopathy, severe hemorrhaging and eventually death. Inasmuch as individual toxins have been evaluated, synergistic mechanism for snake venom pathology are lacking and warranted for antidote development. We hypothesize that precise toxicity evaluation and snake venom analytics of crude/fractionated venom and recombinant toxins will provide a model in which priority can be given to the most toxic venom component(s). To test our hypothesis, we will address (3) Specific Aims: Specific Aim 1: To profile snake venom composition, combinational assessment and intrinsic toxicity. We will purify and characterize snake venom of Crotalid snake species. Characterization will include profiling snake venom to identify the toxins in each fraction and abundance. Students will investigate the mechanism of action different combinations of venom fractions. We will characterize the lethal concentrations/doses of each venom fraction on HUVEC cells, blood coagulation, and will validate the toxicity score for each fraction using an in vivo lethality mouse model. Specific Aim 2: To produce recombinant venom peptides. We will clone these toxins from our collection of cDNA libraries and will generate plasmids and transform competent E.coli cells for protein expression and purification. Development of methods to produce recombinant toxins is essential for antivenom development and investigating toxicity and targets for medically relevant venom peptide. These studies will also be essential to use toxins in solving structures to venom toxins or structures in complexes with known targets. Specific Aim 3: To identify snake venom biomarkers in plasma exosomes. We will explore the “venom-reactome” using novel Evtrap technology and proteomics in discovery-based analysis of snake venom biomarkers from mouse plasma exosomes. Comprehensive snake venom biomarker analysis will shed new light on the pathophysiology, metabolic, biological, cellular and immunological responses to snake venom.


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: 2023 ( Subtotal = -$133,597 )
2023	2022	TEXAS A & M UNIVERSITY KINGSVILLE	700 N UNIVERSITY BLVD	KINGSVILLE	TX	78363	KLEBERG	USA	Biomedical Research and Research Training	001	3	3/29/2023	NON-COMPETING CONTINUATION	-$133,597
2023	2022	TEXAS A & M UNIVERSITY KINGSVILLE	700 UNIVERSITY BLVD	KINGSVILLE	TX	78363	KLEBERG	USA	Biomedical Research and Research Training	000	3	1/19/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = -$133,597

Issue Date FY: 2022 ( Subtotal = $138,000 )
2022	2022	TEXAS A & M UNIVERSITY KINGSVILLE	700 UNIVERSITY BLVD	KINGSVILLE	TX	78363	KLEBERG	USA	Biomedical Research and Research Training	000	3	5/12/2022	NON-COMPETING CONTINUATION	$138,000
														Subtotal = $138,000

Issue Date FY: 2021 ( Subtotal = $138,000 )
2021	2021	TEXAS A & M UNIVERSITY KINGSVILLE	700 UNIVERSITY BLVD	KINGSVILLE	TX	78363	KLEBERG	USA	Biomedical Research and Research Training	000	2	4/19/2021	NON-COMPETING CONTINUATION	$138,000
														Subtotal = $138,000

Issue Date FY: 2020 ( Subtotal = $138,000 )
2020	2020	TEXAS A & M UNIVERSITY KINGSVILLE	700 UNIVERSITY BLVD	KINGSVILLE	TX	78363	KLEBERG	USA	Biomedical Research and Research Training	000	1	4/27/2020	NEW	$138,000
2020	2020	TEXAS A & M UNIVERSITY KINGSVILLE	700 UNIVERSITY BLVD	KINGSVILLE	TX	78363	KLEBERG	USA	Biomedical Research and Research Training	001	1	5/7/2020	NEW	$0
														Subtotal = $138,000

Grand Total All Awards = $280,403

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Evaluation of Toxicity Score and Precise Snake Venom Analytics for Next Generation Antivenom Development

Award Number: SC2GM136606

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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