Thursday, May 2, 2024 5/2/2024

Bottom-up, high-throughput prototyping of extracellular vesicle mimetics using cell-free synthetic biology

Award Number: R01EB034279
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY Bottom-up, high-throughput prototyping of extracellular vesicle mimetics using cell-free synthetic biology Cells secrete extracellular vesicles (EVs) that function as primary messengers of intercellular communication and are studied as promising drug-delivery vehicles and therapeutics. However, the clinical application of native EVs has been hindered by their low production yield, impurity, and inherent heterogeneity. Native EVs contain many biologically active components, such as RNAs and proteins, spread out over numerous subpopulations. This biological complexity is both the strength and the Achilles’ heel of native EVs. While various features of this complexity enable the beneficial therapeutic effects of EVs, it is not clear which plays a dominant role. However, the complex set of proteins and RNAs results in heterogeneous EVs that are challenging to study and use as a standardized treatment. Therefore, separating out and defining the critical biomolecular features from the overall heterogeneous set will allow us to perform quality control of EVs and to reproducibly produce or study EVs. A major bottleneck in finding the critical molecular parts of EVs is the lack of high-throughput methods. To overcome this difficulty, our team will create a synthetic biology-based, cell-free high-throughput discovery platform. The platform will be able to synthesize EV mimetics using a cell-free synthesis approach (Aim 1), coupled with high-throughput examination of EV mimetic potency in vitro (Aim 2). Select EV mimetics will also be investigated using an in vivo model system of neuroprotection and immune modulation (Aim 3). Throughout the study, we will use native mesenchymal stem/stromal cell EVs and neurological diseases as our model system to evaluate the platform. Our work will enable the high-throughput study of EVs for any disease and biological questions of interest. In addition, we will unveil new insights into EVs that address key debated topics in the EV field.


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: 2024 ( Subtotal = $515,936 )
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	2/29/2024	NON-COMPETING CONTINUATION	$515,936
														Subtotal = $515,936

Issue Date FY: 2023 ( Subtotal = $570,556 )
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	1	9/19/2023	SUPPLEMENT FOR EXPANSION	-$89,486
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	1	8/14/2023	SUPPLEMENT FOR EXPANSION	$89,486
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	2/23/2023	NEW	$570,556
														Subtotal = $570,556

Grand Total All Awards = $1,086,492

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Bottom-up, high-throughput prototyping of extracellular vesicle mimetics using cell-free synthetic biology

Award Number: R01EB034279

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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