MANUFACTURING ARTICLES

• How Informal FDA Feedback Is Quietly Driving RNA Capital Allocation

  Subtle FDA signals — especially in pre-IND talks — are quietly shaping RNA investment. Early regulatory feedback on CMC and comparability now drives how investors assess risk and allocate capital.

• Inside Alnylam's Playbook For High Volume siRNA Production

  As one of the first companies to establish a chemoenzymatic ligation platform, Alnylam's Maines and Nechev are in the perfect position to espouse wisdom on the practical aspects and remaining challenges of implementing enzymatic ligation at a large scale. Here in this installment, Maines and Nechev outline what they’ve learned thus far about the science of enzymatic ligation, while also paying credence to the unknowns and existing barriers that, as a frontrunner, Alnylam will inevitably (but willingly) be tasked with facing in the future.

• The "Middle Ground" Advantage: Why Alnylam Is Betting Big On Chemoenzymatic Ligation

  Though conversations are picking up around this hybrid approach, we aren’t exactly known as an industry that embraces risk no-holds barred. While there are a handful of manufacturers and CDMOs who are embracing the hybrid model today, there are many more that are likely to hold out for the next-next gen approach: Fully enzymatic oligo production. However, as Alynlam’s CTO and Chief Quality Officer Tim Maines argued, embarking into the “middle ground” of enzymatic ligation is essential for garnering the step-by-step learnings needed to help us unlock even bigger manufacturing wins in the future. 

• The Evolution Of Oligonucleotide Manufacturing: Engineering Considerations For Scale, Efficiency, And Facility Design

  As oligos move toward larger indications, manufacturing shifts from chemistry alone to facility design—balancing scale, solvent safety, cost, and flexibility as SPOS, slurry, and enzymatic paths converge.

• 2026 RNA Investment Landscape: Recent Deals, IPOs, And Venture Trends

  As RNA investing matures, capital is flowing toward delivery, durability, and regulatory credibility. This column breaks down the deals, IPO signals, and venture theses shaping RNA’s 2026 winners—and why.

• Innovations In The Oligonucleotide Supply Chain: Regulatory Considerations For Materials, Manufacturing, And Lifecycle Control

  Oligonucleotide therapeutics have rapidly advanced into late-stage and commercial development, shifting regulatory focus toward the maturity of manufacturing and supply chain control rather than therapeutic novelty. Regulatory success now depends on how effectively sponsors translate innovative chemistries into well-characterized, scalable, and sustainable materials and processes.