RNA Synthesis via Ligation for Improved Scalability and Reduced Manufacturing Cost
During traditional RNA synthesis, each nucleotide added to the growing oligonucleotide compounds the coupling errors, which decreases the yield of longer RNAs. By utilizing a ligation approach, multiple short, single-stranded RNA (ssRNA) fragments can be ligated together to form the desired double-stranded RNA (dsRNA) duplex. RNA synthesis via ligation can create a higher purity and yield, which improves scalability and significantly reduces manufacturing cost.
Solid phase RNA synthesis comprises a cascade of eight sequential chemical reactions for each nucleotide addition. Since chemical reactions are inherently less than 100% efficient, each nucleotide added to the growing oligoribonucleotide chain compounds coupling errors, decreasing the final purity and yield of full-length siRNA. Rather, by utilizing an enzymatic approach, multiple short, single-stranded RNA (ssRNA) fragments can be ligated together to form the desired double-stranded RNA (dsRNA) duplex.
Codexis’ RNA Ligase Screening and Optimization Services serve as a “bridge” to introduce enzymatic solutions into your traditional chemical manufacturing process, enabling higher purity and yield, improving scalability and reducing purification costs.
Engineered dsRNA Ligases Can Efficiently Scale siRNA Manufacturing
Even though ligation is being increasingly adopted as an approach, wild-type dsRNA ligases are often expensive and inefficient on challenging substrates. With a library of engineered ligases available today, Codexis can shorten and de-risk the ligase optimization cycle so that you can realize the benefits of enzymatic approaches sooner:
- Faster process development
- Improved manufacturability
- Custom pharma manufacturing expertise
- Higher scalability
- Complements solid state synthesis
Scalability
Engineered ligases enable optimized process conditions with lower enzyme loading at high substrate concentrations while maintaining high ligation efficiency. Ligation complements solid phase synthesis by enabling scaling of promising assets already in clinical development. Ligase selectivity streamlines downstream purifications, thereby improving overall API yield, increasing manufacturing efficiencies, and driving down costs.
Process Development
Leverage our deep catalog of ligase variants to enable rapid screening across challenging substrate designs. In addition, our team of technical experts is available to consult on RNA fragment design and recommend reaction conditions ensuring optimal outcomes for your siRNAasset.