# Development of superior polymerases for next-generation mRNA therapeutic & vaccine manufacturing

> **NIH NIH R44** · PRIMROSE BIO, INC. · 2020 · $1,152,047

## Abstract

Project Summary/Abstract
 Messenger ribonucleic acid (mRNA) plays key roles in cells and organisms as a carrier of
protein-coding information and as a regulator of gene expression. The pharmaceutical industry has
begun to exploit the many natural functions of mRNA to develop novel therapeutics and vaccines,
which promise high efficacy and great flexibility in the prevention and treatment of diseases
ranging from cancers and infectious diseases such as hepatitis and HIV to genetic diseases such
as cystic fibrosis and rare diseases caused by heritable genetic defects.
 The expanded effort in mRNA therapeutics and mRNA vaccines has created a new demand for
mRNA molecules manufactured in large quantities to precise specifications. In particular, the need
to create mRNA molecules >1kb in length that are free of unwanted side products, and to
incorporate modified nucleotides for more efficient delivery, higher stability and better clinical
efficacy, has compounded this manufacturing problem. Although RNAs can be produced
enzymatically in vitro with the use of specialized RNA polymerases, the enzymes widely used to
produce RNA for R&D purposes are not suited for the demanding specifications that apply to RNA
molecules intended for mRNA therapeutics and vaccines. A new class of enzymes, highly
optimized for synthesis of long RNAs with specific sequences and structures, need to be created to
meet this new demand.
 In a Phase I feasibility project, Primordial Genetics discovered and tested 53 novel RNA
polymerases of which 13 were found to be superior to the current enzymes used for RNA
manufacturing. On the strength of our Phase I results, the company began to forge connections to
RNA therapeutics companies who are very interested in testing our new enzymes.
 In the proposed Phase II project, we will improve four of these enzymes, characterize the
activity of six improved enzymes in detail, and prepare methods and datasets for using these
enzymes for clinical mRNA manufacturing. Our goal is to create enzymes that can meet the varied
needs for manufacturing a diversity of mRNA sequences, sizes and chemical structures
represented in mRNA vaccines and mRNA therapeutic products under development. The enzymes
discovered and improved in this work will be directly useful for mRNA manufacturing applications,
and will be licensed or sold to companies developing mRNA vaccines and therapeutics as well as
companies building RNA manufacturing capabilities.

## Key facts

- **NIH application ID:** 10082063
- **Project number:** 2R44GM131548-02
- **Recipient organization:** PRIMROSE BIO, INC.
- **Principal Investigator:** Helge Zieler
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,152,047
- **Award type:** 2
- **Project period:** 2018-09-17 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10082063

## Citation

> US National Institutes of Health, RePORTER application 10082063, Development of superior polymerases for next-generation mRNA therapeutic & vaccine manufacturing (2R44GM131548-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10082063. Licensed CC0.

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