# Human Ribonuclease as a Cytotoxin

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2022 · $340,527

## Abstract

PROJECT DESCRIPTION
Human pancreatic ribonuclease (RNase 1) is a secretory enzyme that can block
the flow of biochemical information by catalyzing the cleavage of cellular RNA.
Our intent is to use ideas and methods from biological chemistry, molecular
biology, and cell biology to reveal key mechanistic aspects of the cytotoxicity of
human RNase 1 in physiological and (potentially) clinical settings. During the
next grant period, this intent will be achieved in four Specific Aims.
Specific Aims. In Aim 1, we will determine whether the complex of RNase 1
with the cytosolic ribonuclease inhibitor protein (which has femtomolar affinity
for RNase 1) acts as a “sensor” for oxidative damage within a human cell. In
Aim 2, we will determine the structural and physiological roles of the N-linked
glycans that are installed on RNase 1. In Aim 3, we will develop an RNase 1
zymogen as a “prodrug” that is activated by matrix metalloproteases. In Aim 4,
we will evaluate RNase 1 as an endogenous antimicrobial agent.
Significance. The results of the research proposed herein will provide a detailed
biochemical understanding of the cytotoxic activity of RNase 1, and could
ultimately lead to new chemotherapeutic agents based on an endogenous human
enzyme.

## Key facts

- **NIH application ID:** 10433859
- **Project number:** 5R01CA073808-25
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Ronald T Raines
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $340,527
- **Award type:** 5
- **Project period:** 1997-07-10 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10433859

## Citation

> US National Institutes of Health, RePORTER application 10433859, Human Ribonuclease as a Cytotoxin (5R01CA073808-25). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10433859. Licensed CC0.

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