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Controlled Delivery of Plasmid DNA via Low-Temperature Ion Deposition

Award Number: R01EB023878
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/08/2020
PERIOD OF PERFORMANCE END DATE: 05/31/2024

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Controlled Delivery of Plasmid DNA via Low-Temperature Ion Deposition - The long-range goal of this research program is the development of efficient in vivo gene delivery systems. The goal of this specific project is the development of an improved minimally invasive system for the delivery of plasmid DNA to the skin. Skin is easily accessibility which makes it an excellent target for gene therapy applications whether it is for directly treating cutaneous diseases or utilizing the skin as a depot for delivering proteins directly to the circulation for systemic therapy. To take advantage of the easy accessibility of the skin it is critical to develop non-contact approaches that are a simple and direct in vivo method to deliver DNA and can be accomplished in a minimally invasive way. We have been working on developing such approaches and previously developed devices and protocols that utilized electrotransfer for this delivery. While these devices have worked effectively and can accomplish this in a relatively non-invasive manner, it is still necessary to have contact between the electrodes and the tissue target. In addition, the applied voltages needed to achieve delivery on some occasions may cause cellular or tissue damage or potential discomfort. It is critical to develop an alternative approach that can work as well as electrotransfer but do it without the contact. An additional consideration is to develop an approach and/or device that will allow for better control of delivery and move towards a more predictable and reproducible pattern of expression. To accomplish this, we propose to utilize a non-thermal atmospheric pressure plasma device that can permeabilize cells and facilitate plasmid DNA uptake. We hypothesize that delivery is achieved by ion deposition on the surface of the target tissue and that if the level of ion deposition is regulated then expression levels can be controlled. The novel plasma device to be further developed and evaluated is based on nanosecond pulsed air plasmas. Using this approach will allow us to develop a small portable device that could be battery operated. This will be a non-contact delivery device that will minimize or eliminate potential discomfort and/or cellular damage. The following specific aims will be performed as part of this project. 1) To evaluate non-thermal atmospheric plasma devices for controlled production of ions that can be deposited on tissue surface; 2) To evaluate NTAP devices producing various level of ions for delivery of plasmid DNA to the skin and to determine the duration of maximal expression levels and to determine if this time can be increased by performing multiple delivery procedures; and 3) to determine if the system established in the first two aims can deliver plasmids encoding therapeutic proteins. The investigators have extensive expereince in developing non-thermal plasma devices and gene transfer so are well suited to successfully complete the study.


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 = -$610 )
2025	2022	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	5	12/9/2024	NON-COMPETING CONTINUATION	-$610
														Subtotal = -$610

Issue Date FY: 2022 ( Subtotal = $416,667 )
2022	2022	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	5	5/25/2022	NON-COMPETING CONTINUATION	$416,667
														Subtotal = $416,667

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	6/3/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $416,804 )
2020	2020	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	005	4	4/29/2020	NON-COMPETING CONTINUATION	$416,804
2020	2019	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	004	3	4/13/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$211,420
2020	2019	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	3	1/14/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$422,444
2020	2019	OLD DOMINION UNIVERSITY	5115 HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	1/14/2020	NON-COMPETING CONTINUATION	-$422,444
2020	2019	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVE	TAMPA	FL	33620	HILLSBOROUGH	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	3	2/3/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2020	2018	OLD DOMINION UNIVERSITY	5115 HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	003	1	4/13/2020	NEW	-$211,420
														Subtotal = $416,804

Issue Date FY: 2019 ( Subtotal = $422,444 )
2019	2019	OLD DOMINION UNIVERSITY	5115 HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	5/23/2019	NON-COMPETING CONTINUATION	$422,444
														Subtotal = $422,444

Issue Date FY: 2018 ( Subtotal = $424,746 )
2018	2018	OLD DOMINION UNIVERSITY	5115 HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	8/28/2018	NEW	$424,746
														Subtotal = $424,746

Grand Total All Awards = $1,680,051

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Controlled Delivery of Plasmid DNA via Low-Temperature Ion Deposition

Award Number: R01EB023878

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/08/2020

PERIOD OF PERFORMANCE END DATE: 05/31/2024

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