# Repurposing Mycobacterium tuberculosis tRNase toxins for cancer chemotherapy

> **NIH NIH R21** · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · 2022 · $236,333

## Abstract

Project Summary
The genome of the bacterium that causes tuberculosis, Mycobacterium tuberculosis (Mtb), harbors an
astonishingly large number of specialized growth regulating toxins. We and others have discovered that many
of these Mtb toxins are highly selective tRNases with properties that make them attractive candidates for cancer
treatment on their own or as protein-conjugated immunoRNases. There is one RNase to go into clinical trials for
treatment of cancer, Onconase. However, the Mtb tRNase toxins have much higher intrinsic specificity than the
poorly characterized enzymatic activity of Onconase. The unprecedented target selectivity of these Mtb tRNase
toxins is important because earlier tRNA microarray expression studies revealed significant increases in a few
functional, full length tRNAs in patient-derived breast tumor samples. These tRNA species are thought to be
upregulated in order to accommodate higher demand when cells are reprogrammed to produce one or more
cancer-promoting proteins rich in this particular amino acid. Therefore, Mtb tRNase toxins constitute a large new
untapped reservoir of highly specialized tRNases, each endowed with the ability to recognize a single tRNA as
substrate. In this exploratory R21 proposal in response to FOA PAR-19-194 Microbial-based Cancer Therapy -
Bugs as Drugs, we hypothesize that these specialized toxins can ultimately be exploited for cancer treatment
because they are predicted to cleave and disable tRNAs required for efficient translation of pro-oncogenic
proteins. The three specific Aims define the specificity of six of these tRNase toxins in human breast cancer cell
lines and tissues.

## Key facts

- **NIH application ID:** 10354376
- **Project number:** 1R21CA267852-01
- **Recipient organization:** RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
- **Principal Investigator:** NANCY ANN WOYCHIK
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $236,333
- **Award type:** 1
- **Project period:** 2021-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10354376

## Citation

> US National Institutes of Health, RePORTER application 10354376, Repurposing Mycobacterium tuberculosis tRNase toxins for cancer chemotherapy (1R21CA267852-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10354376. Licensed CC0.

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