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Mechanistic insights on structure, topology and radiation effects on RNA nanomedicines

Award Number: R01CA270783
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/10/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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Mechanistic insights on structure, topology and radiation effects on RNA nanomedicines - PROJECT ABSTRACT RNA therapeutics and their corresponding nanomedicines are poised to rapidly change the landscape of healthcare. To address needs in various diseases, RNA-based technologies must function in vivo with biological interactions at various levels from whole body (systemic biodistribution and immunological) to tissues and organs, to intracellular trafficking and endosomal release. Unfortunately in oncology, efficient systemic delivery of lipid nanoparticles (LNPs) to solid tumors has been plagued by poor tissue accumulation largely due to a gap in the knowledge of fundamental interactions between these materials and biological systems. Here we propose to investigate the structure-activity-relationship (SAR) of nanoparticle carriers through use of a chemically and topologically diverse library of lipopolymers fine- tuning the biointerface of RNA-LNP. Utilizing a combined barcoding and serial in-depth mechanistic assays, we will test our central hypothesis that a defined series of first-principles relationships govern the biophysical interactions of LNPs in vivo. Using cancer models, we will correlate the spatial and temporal accumulation of mRNA at target tissues and cells with biophysicochemical properties of the LNP biointerface. The goal of this project is to establish a framework of physiochemical properties to guide the development of RNA-LNP based cancer nanomedicines. We will achieve this goal by the pursuing the following aims: Aim 1 - Structural and topological fine-tuning of LNPs biointerface. Aim 2 - Elucidate the biological interactions of LNPs with respect to whole-body, tissue-level, and intracellular distributions. Aim 3 - Investigate the biological interaction and efficacy of LNPs in the context of multimodal breast cancer therapy. The immediate outcomes of this research will be applied toward advancing the use of nanotechnology in oncology. Our project will yield a critical and detailed understanding of the role the LNP biointerface and its effects on the fate of LNPs in complex biological systems as well as their efficacy. This invaluable knowledge would greatly aid in future developments in nanomedicine as a whole.


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: 2025 ( Subtotal = $502,323 )
2025	2025	OREGON STATE UNIVERSITY	1500 SW JEFFERSON AVE	CORVALLIS	OR	97331	BENTON	USA	Cancer Detection and Diagnosis Research	000	3	1/9/2025	NON-COMPETING CONTINUATION	$502,323
														Subtotal = $502,323

Issue Date FY: 2024 ( Subtotal = $530,230 )
2024	2024	OREGON STATE UNIVERSITY	1500 SW JEFFERSON AVE	CORVALLIS	OR	97331	BENTON	USA	Cancer Detection and Diagnosis Research	001	2	4/17/2024	NON-COMPETING CONTINUATION	$27,907
2024	2024	OREGON STATE UNIVERSITY	1500 SW JEFFERSON AVE	CORVALLIS	OR	97331	BENTON	USA	Cancer Detection and Diagnosis Research	000	2	12/22/2023	NON-COMPETING CONTINUATION	$502,323
														Subtotal = $530,230

Issue Date FY: 2023 ( Subtotal = $570,260 )
2023	2023	OREGON STATE UNIVERSITY	1500 SW JEFFERSON ST	CORVALLIS	OR	97331	BENTON	USA	Cancer Detection and Diagnosis Research	000	1	1/10/2023	NEW	$570,260
														Subtotal = $570,260

Grand Total All Awards = $1,602,813

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Mechanistic insights on structure, topology and radiation effects on RNA nanomedicines

Award Number: R01CA270783

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/10/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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