RNA Manufacturing at Codexis

RNA Manufacturing

Aiding the manufacture of RNA

When manufacturing RNA for therapeutic applications, the process ideally delivers high yields and minimizes unwanted byproducts, while being economically sound. Codexis enzymes are developed to deliver higher performance in the attributes manufacturers and therapeutic developers care about most, from maintaining yield to process efficiencies that improve economies of scale.

Codexis’ ECO Synthesis™ technology (Enzyme-Catalyzed Oligonucleotide Synthesis) is a proprietary new synthesis platform being developed for manufacturing modified-RNA oligonucleotide therapeutics, such as small interfering RNA (siRNA) and antisense oligonucleotides (ASO), at large-scale.

IVT Workflow Overview

IVT Workflow - Plasmid Template Manufacturing chart

In vitro transcription (IVT) is a method used to manufacture large quantities of mRNA. IVT is accomplished through either co-transcriptional or post-transcriptional capping (sometimes called enzymatic capping). In co-transcriptional capping, wild-type T7 (WT T7) RNA polymerase can achieve ~95% capping efficiency when optimized with trinucleotide cap analogs, and less than 80% capping efficiency with dinucleotide cap analogs (such as ARCA). Given the loss in capping efficiency, manufacturers prefer post-transcriptional capping with Vaccinia Capping Enzyme (VCE) when dinucleotide caps are used, as it can achieve >95% capping, but this also introduces additional process and purification steps.

Codexis enzymes are designed to address these trade-offs manufacturers face to improve overall process efficiency and quality. The Codex® HiCap RNA Polymerase is the first enzyme engineered to improve co-transcriptional capping efficiency using either trinucleotide or dinucleotide cap analogs, while achieving >95% capping efficiency with both cap analog formats.

Read Engineered T7 RNA Polymerase manuscript

Codex® HiCap RNA Polymerase

Improve mRNA capping efficiency

Produce capped synthetic mRNA at high yield and low immunogenicity with Codex® HiCap RNA Polymerase. Greater capping efficiency and the production of less double-stranded RNA byproduct deliver exceptional IVT results.

Read more about Codex® HiCap RNA Polymerase

Scientific Highlights

An engineered T7 RNA polymerase for efficient co-transcriptional capping

Mathew Miller, Principal Scientist at Codexis, presented a poster at the 2022 Intl mRNA Health Summit highlighting how an engineered T7 RNA polymerase can overcome common challenges with capping efficiency and dsRNA impurities in IVT manufacturing of mRNA.

View poster

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