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

> **NIH NIH R21** · J. DAVID GLADSTONE INSTITUTES · 2023 · $283,500

## Abstract

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.

## Key facts

- **NIH application ID:** 10589891
- **Project number:** 5R21EB031393-02
- **Recipient organization:** J. DAVID GLADSTONE INSTITUTES
- **Principal Investigator:** Seth Lawler Shipman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $283,500
- **Award type:** 5
- **Project period:** 2022-03-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10589891

## Citation

> US National Institutes of Health, RePORTER application 10589891, RetroDecoys: Temporally-regulated and cell type selective technology for transcriptional control (5R21EB031393-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10589891. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*