# Synthetic biology for controlled release

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2021 · $338,366

## Abstract

Abstract:
The prospects for the facile biosynthesis of drugs coupled with the manipulation of the human microbiome is
fraught with therapeutic possibilities. However, the same caveats that exist for the delivery of drugs via ingestion
or injection apply to the microbial delivery of drugs. In particular, a therapeutic regime for administration must
be established that is efficacious but not harmful. For years, one means of ensuring the longer-term delivery of
drugs in specified amounts has been to develop particles, pills, or patches that maintain the controlled or
sustained release of drugs into the system. We propose a new paradigm for controlled release, in which
controlled release is driven by controlled biosynthesis, which in turn relies on an underlying, modular regulatory
mechanism. We establish a separate ‘engine’ for the expression of therapeutic cargoes, relying on the highly
orthogonal T7 RNA polymerase (T7 RNAP), and develop a variety of circuits that lead to regulated gene
expression in different patterns of therapeutic relevance, such as homeostatic production of constant
concentrations of a drug (Aim 1). We then apply this ‘engine’ to the production of the amino acid L-DOPA in a
known probiotic strain, E. coli Nissle (Aim 2). And then finally the controlled production circuitry in the probiotic
species is introduced into mouse models in order to determine how programmed regulatory circuitry can impact
the pharmacokinetics and pharmacodynamics of a drug in an organism (Aim 3). The strains are ultimately tested
in a chronic progressive degenerative MitoPark mouse model of Parkinson’s disease currently being used in our
collaborator’s laboratory at Iowa State University (Aim 3.3).

## Key facts

- **NIH application ID:** 10113359
- **Project number:** 5R01EB026533-03
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Andrew D Ellington
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $338,366
- **Award type:** 5
- **Project period:** 2019-05-04 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10113359

## Citation

> US National Institutes of Health, RePORTER application 10113359, Synthetic biology for controlled release (5R01EB026533-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10113359. Licensed CC0.

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