# Systems for Dramatically Improved Synthetic RNA

> **NIH NIH R01** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2021 · $306,860

## Abstract

Project Summary
A wide variety of RNA researchers synthesize their RNA using the enzyme T7 RNA polymerase, as this
enzyme is robust and can yield large quantities of RNA, at any length scale. However, undesired
products typically contaminate the desired RNA, in often unpredictable ways. This is perhaps most
impactful currently in the mRNA therapeutics field, where contaminating double stranded RNAs can
trigger a potentially lethal innate immune response, but contaminants almost certainly impact other
studies as well, from basic research in cell and molecular biology and biochemistry/biophysics, to
synthetic biology, to RNA nanotechnology. Gel purifications are tedious, low yield, and imperfect
(indeed, the darkest band on the gel may not be the correct product, and even the correct length RNA
pool can be heterogeneous!). Longer RNA impurities derive from correct RNA, reducing yields at
synthesis, and can be distributed across a wide range of lengths, making gel analysis problematic.
Building on new mechanistic understandings, this project will develop systems that limit the conditions
that give rise to these impurities, specifically by inhibiting the off-pathway reactions, and will develop
simple affinity purification approaches – all with an aim towards achieving monodisperse RNAs of
defined length and sequence. Sensitive analytical and functional assays for success will be developed
and applied to guide design. Tools will be developed with an eye towards broad adoption by a variety of
researchers.

## Key facts

- **NIH application ID:** 10127670
- **Project number:** 5R01GM134042-02
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** Craig T Martin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $306,860
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10127670

## Citation

> US National Institutes of Health, RePORTER application 10127670, Systems for Dramatically Improved Synthetic RNA (5R01GM134042-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10127670. Licensed CC0.

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