ECO Synthesis™ Technology at Codexis

ECO Synthesis™ Technology

RNAi Therapeutics Overview

Addressing sustainability of oligonucleotide synthesis

ECO SynthesisTM technology (Enzyme-Catalyzed Oligonucleotide Synthesis) is a proprietary new synthesis platform that is being developed for manufacturing RNA oligonucleotide therapeutics at scale. By replacing crucial chemical processes with enzymatic methods, ECO SynthesisTM technology is envisioned to address sustainability and scalability challenges of oligonucleotide manufacturing.

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graphic showing Enzyme-Catalyzed Oligonucleotide Synthesis

ECO Synthesis™ technology is driven by multiple novel enzymes working as a system to synthesize modified nucleic acids efficiently. The core iterative oligo extension cycle leverages a proprietary terminal deoxynucleotidyl transferase (TdT) enzyme engineered to incorporate common 2’-modified nucleotides, including 2’-F, 2’-OMe, and backbone-modified alpha-phosphorothioate nucleotides, critical for therapeutic RNA applications. Deblocking is achieved enzymatically to close the cyclical process.

TdT: the enabling enzyme

An engineered TdT is the linchpin of ECO SynthesisTM technology, fine-tuned for promiscuity and activity. The result is a highly specialized enzyme with the ability to incorporate required modified nucleotides with high efficiency and low bias.

Enzymatic supply of monomers

ECO SynthesisTM technology requires 3’-blocked-2’-modified NTPs as monomers, which are traditionally synthesized chemically. Using a biocatalytic cascade, Codexis will synthesize these key monomers from nucleoside precursors, creating a reliable and more sustainable supply for the iterative oligo extension process.

Sustainability impact

Envisioned to meet multi-kg annual demand, the combination of catalytic enzyme activity and the use of aqueous reaction conditions will tackle major drawbacks of chemical synthesis methods.

Shifting the paradigm for siRNA synthesis

Our CodeEvolver® technology platform and experience in enzyme manufacturing come together to enable ECO Synthesis™ technology, with a mission to address the manufacturing obstacles of therapeutic oligonucleotides such as small interfering RNA (siRNA) and antisense oligonucleotides (ASO). The technology strives to provide a transformational alternative to phosphoramidite chemistry and the substantial amount of chemical waste produced.

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