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RetroDecoys: Temporally-regulated and cell type selective technology for transcriptional control

Award Number: R21EB031393
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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RetroDecoys: Temporally-regulated and cell type selective technology for transcriptional control - Project Summary/Abstract Transcription factors orchestrate the most dynamic processes in cells – from producing cascades of antiviral and antibiotic resistance proteins to differentiation and metastasis. A change in the abundance of even a single transcription factor can induce a pattern of gene expression that fundamentally alters the transcriptome and physiology of a cell. Interestingly, the effect that a transcription factor has on gene expression is a function of both the abundance of the factor itself as well as the abundance of its binding site in DNA. As the number of DNA binding sites increases, the effect of each transcription factor molecule decreases. Yet, in cells, protein abundance changes and the number of DNA binding sites is static, so the transcription factor amount is the only point of dynamic control. We aim to engineer and test a molecular technology that will produce abundant transcription factor binding sites in DNA in vivo, on demand. These DNA molecules will compete for occupancy by the transcription factors, thereby antagonizing their action on endogenous genes. To build this technology, we will engineer retroelements to reverse transcribe the target site under the control of inducible and cell-type specific promoters. These elements can be integrated into genetic circuits as programmable parts for synthetic biology and a means to exert control over a transcriptome that is responsive to a cell's state. They also enable antagonism of transcription factors that currently have no small molecule antagonist. We will validate this approach in two clinically relevant models: cancer progression and antibiotic resistance.


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 = $0 )
2024	2023	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	7/24/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $283,500 )
2023	2023	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	12/22/2022	NON-COMPETING CONTINUATION	$255,150
2023	2023	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	1/31/2023	NON-COMPETING CONTINUATION	$28,350
														Subtotal = $283,500

Issue Date FY: 2022 ( Subtotal = $236,250 )
2022	2022	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	3/10/2022	NEW	$212,625
2022	2022	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	1	7/8/2022	NEW	$23,625
														Subtotal = $236,250

Grand Total All Awards = $519,750

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RetroDecoys: Temporally-regulated and cell type selective technology for transcriptional control

Award Number: R21EB031393

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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