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Structure-Property-Function Relationship in mRNA/CARTs for Targeted mRNA Delivery

Award Number: F32AI176755
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/01/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Structure-Property-Function Relationship in mRNA/CARTs for Targeted mRNA Delivery - Project Summary/Abstract The proposed research will improve the understanding of structure-property-function relationships in formulations of charge-altering releasable transporter (CART) gene delivery vectors. These materials demonstrate remarkable efficiency for mRNA transfection with low cytotoxicity due to charge-neutralizing degradative chemistry and have shown remarkable selectivity towards different organs in vivo depending on the chemical structure of the CART. A predictive understanding of how chemical variation affects nanostructure and biological activity will be established. If successful, a set of design rules for CARTs will guide the optimization of mRNA/CART complexes for improved cellular transfection and catered cellular/organ selectivity enabling the development of site-specific CART / RNA therapeutics. The fellow will be the first to perform detailed structural and dynamic studies using advanced cryogenic transmission electron microscopy (cryoEM) and in situ X-ray scattering, illuminating the morphological properties of mRNA/CART nanoparticles. Additionally, this proposal will establish if nanostructure variation arises from changes in formulation technique and CART chemical structures (cation, lipid) and relate these nano-structural variation to differences in biological function. The fellow will develop microfluidic mixing protocols (t-mixer) and screen mRNA/CARTs with differing sizes/morphologies in vitro with cell cultures to establish correlations between functional outcome and nanostructure. In addition to cryoEM and scattering, supplementary measurements of zeta potential, size, phase, thermal transitions, supramolecular interactions, etc. will be carried out to determine the effect physico-chemical properties has on nanostructure in different CART formulations. In separate future research not covered by this proposal, the most distinct mRNA/CARTs will be further studied with in vivo experimentation in mouse models with our collaborators. The fellow will also receive formal and informal training in the responsible conduct of research, teaching, career development skills applicable to their future career goals of becoming a research professor and participate in outreach and mentoring. These studies will take place in a highly interdisciplinary training environment at Stanford University in the lab of Prof. Robert Waymouth, in close collaboration with Dr. Christopher Tassone at SSRL (SLAC national laboratory).


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 = $75,520 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	000	3	12/9/2025	NON-COMPETING CONTINUATION	$75,520
														Subtotal = $75,520

Issue Date FY: 2025 ( Subtotal = $78,052 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	000	2	11/18/2024	NON-COMPETING CONTINUATION	$76,828
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	001	2	7/24/2025	NON-COMPETING CONTINUATION	$1,224
														Subtotal = $78,052

Issue Date FY: 2024 ( Subtotal = $76,408 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	001	1	12/1/2023	NEW	$0
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	002	1	5/13/2024	NEW	$5,224
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	000	1	12/1/2023	NEW	$71,184
														Subtotal = $76,408

Grand Total All Awards = $229,980

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Structure-Property-Function Relationship in mRNA/CARTs for Targeted mRNA Delivery

Award Number: F32AI176755

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/01/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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