# Cancer-specific metabolites as cues to engineer and target anti-tumor therapeutic bacteria

> **NIH NIH R21** · CLEVELAND CLINIC LERNER COM-CWRU · 2022 · $188,169

## Abstract

Abstract
With the ongoing advances in synthetic biology, the application of therapeutic bacteria for cancer treatment is
now closer to becoming a reality. Achieving this goal, however, still needs better targeting of the therapeutic
bacteria towards the cancer sites to improve the efficacy and safety of the treatment. Here, we propose to use
a key cancer metabolite produced in colorectal cancers and other tumors as a cue to activate genetic circuits
inside the therapeutic bacteria to control those bacteria and target them to the cancer site. To achieve this
goal, we are going to clone the naturally occurring transcriptional regulator for this metabolite into
engineered therapeutic E. coli and optimize its performance. In parallel, we will employ specific RNA
aptamers which we already developed for this metabolite, to build synthetic riboswitches to control protein
expression in the engineered Escherichia coli strain. Subsequently, these two tools; the transcription
regulator, and the synthetic riboswitches, will be used in combination to build genetic circuits inside the
engineered E. coli strain. These genetic circuits will then 1) Direct the engineered E. coli (along this key
metabolite concentration gradient) towards the tumor site through controlling its motility, 2) Induce the
attachment of this E. coli to the tumor cells, and 3) Induce the production of a therapeutic molecule within the
tumor microenvironment in response to this key metabolite.
During the time frame of this grant, we will be working on developing these E. coli genetic circuits which can
respond to this metabolite at the physiologically relevant concentrations and we are going to test these
engineered E. coli on cancer cell lines. Future work, which will be pursued through subsequent grants, will
involve trying these engineered bacteria in mice models for colon cancer.

## Key facts

- **NIH application ID:** 10526594
- **Project number:** 1R21CA267711-01A1
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Mohammed Dwidar
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $188,169
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10526594

## Citation

> US National Institutes of Health, RePORTER application 10526594, Cancer-specific metabolites as cues to engineer and target anti-tumor therapeutic bacteria (1R21CA267711-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10526594. Licensed CC0.

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