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SMART NANPs: new molecular platform for communication with human immune system and modulation of therapeutic responses

Award Number: R35GM139587
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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SMART NANPs: new molecular platform for communication with human immune system and modulation of therapeutic responses - Principal Investigator/Program Director (Last, First, Middle): Afonin, Kirill, A PROJECT SUMMARY What if healthcare providers were equipped with biocompatible, biodegradable, robust, and affordable treatment options that combine therapeutic modalities with controlled mechanisms of action? What if this versatile technology had learning capacity and could be educated to recognize patient-specific diseases and interfere with their progression by redirecting fundamental cellular processes? What if the very same formulation could offer an additional means of control over patients’ immune responses and further advance favorable therapeutic outcomes with minimal toxicities? These next generation therapies would then become a game changer in helping to prevent, detect, diagnose, and treat diseases and disabilities at their source. With the support from MIRA (R35) funding, we envision a data-driven platform, SMART NANPs (specific, modular, adjustable, reproducible, and targeted nucleic acid nanoparticles), encoded by self-assembling nucleic acids. By controlling the flow of genetic information across all forms of life, nucleic acids have become instrumental in acquiring new knowledge about major cellular processes and origins of diseases. Besides their diverse biological roles, these biopolymers can be programmed into NANPs with specified physicochemical properties and functionalities that dictate NANPs’ biological actions with endless possibilities for reprogramming cellular behavior through molecular signaling. We recently discovered that different architectural parameters and compositions of NANPs, delivered to primary human immune cells, can activate monocytes and dendritic cells to produce type I and type III interferons. This pioneering work on NANPs’ immunorecognition highlighted an unforeseen clinical application for this technology in the field of vaccines and immunotherapy. A defined structure-function relationship for any given NANP would then allow conditional actuation of its immunorecognition or any other therapeutic activity through a set of embedded architectural codes. With this notion, we introduced two orthogonal concepts of therapeutic NANPs which can be conditionally activated in human cancer cells to release pre-programmed therapeutics. By uniting these breakthroughs and other preliminary findings from my lab, as highlighted in the current application, and integrating them into a unified network of SMART NANPs with programmable control of biodistribution, immunological activity, and therapeutic modules, we will advance the current repertoire of therapies against infectious diseases and cancers (through NANP-based vaccines and immunotherapies), cardiovascular diseases (through regulated coagulation by thrombin-targeting NANPs), and address drug overdose and safety issues (through the biodegradable nature of NANPs and their controlled deactivation). To maximize the successful translation of this technology, the proposed program will employ a multidisciplinary approach that spans the fields of nucleic acid nanotechnology, immunology, drug delivery, translational oncology, and machine learning. The long-term goal of this program is to elevate SMART NANPs to the level of clinical use.


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 = $345,545 )
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Biomedical Research and Research Training	001	5	1/23/2025	NON-COMPETING CONTINUATION	$345,545
2025	2024	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Biomedical Research and Research Training	000	4	11/13/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $345,545

Issue Date FY: 2024 ( Subtotal = $399,286 )
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Biomedical Research and Research Training	001	4	5/16/2024	NON-COMPETING CONTINUATION	$38,439
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Biomedical Research and Research Training	000	4	12/15/2023	NON-COMPETING CONTINUATION	$345,952
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Biomedical Research and Research Training	002	4	6/6/2024	SUPPLEMENT FOR EXPANSION	$14,895
														Subtotal = $399,286

Issue Date FY: 2023 ( Subtotal = $503,020 )
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Biomedical Research and Research Training	002	3	6/27/2023	SUPPLEMENT FOR EXPANSION	$118,201
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Biomedical Research and Research Training	001	3	4/6/2023	NON-COMPETING CONTINUATION	$38,482
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Biomedical Research and Research Training	000	3	1/16/2023	NON-COMPETING CONTINUATION	$346,337
														Subtotal = $503,020

Issue Date FY: 2022 ( Subtotal = $385,224 )
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Biomedical Research and Research Training	001	2	6/22/2022	NON-COMPETING CONTINUATION	$38,523
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Biomedical Research and Research Training	000	2	1/27/2022	NON-COMPETING CONTINUATION	$346,701
														Subtotal = $385,224

Issue Date FY: 2021 ( Subtotal = $141,556 )
2021	2021	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Biomedical Research and Research Training	000	1	1/22/2021	NEW	$141,556
														Subtotal = $141,556

Grand Total All Awards = $1,774,631

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SMART NANPs: new molecular platform for communication with human immune system and modulation of therapeutic responses

Award Number: R35GM139587

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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