Securing the oligonucleotide supply chain: addressing raw material risks, environmental pressures, and geopolitical factors

Louis Diorazio is Senior Principal Scientist for New Modalities in AstraZeneca’s Chemical Development group based in Macclesfield, UK. He obtained a BSc and PhD from Imperial College, London, on aromatic fluorination, followed by postdoctoral studies with Prof. Phil Magnus in the field of natural product synthesis. He has 32 years of industry experience across small molecules and new modalities from discovery activities through to commercialisation. A long-term feature of his activities has been driving a development culture focused on delivering high-impact, sustainable processing through innovation and collaboration.

Dennis Rhodes is an Associate Director in Analytical Development and Quality Control at Ionis Pharmaceuticals, where he has worked since 2008, and leads the raw materials group that supports GMP release and control of starting materials for oligonucleotide therapeutics. His work focuses on UHPLC/MS method development and validation for nucleoside phosphoramidites and other oligonucleotide starting materials, impurity profiling, and establishing robust control strategies and specifications for complex raw and starting materials. Dennis previously served as an expert advisor on oligonucleotide starting materials through his work with the USP oligonucleotide committee, helping to shape emerging guidance on analytical methods and control strategies for this class of therapeutics.

Shubh has 15 years of experience in oligonucleotide chemistry and drug development. At Agilent Technologies, he developed synthetic technologies enabling commercial RNA-based products, and in leadership roles at miRagen and CAMP4, he advanced multiple oligonucleotide programs from discovery to GMP manufacturing and regulatory submissions. His expertise spans medicinal chemistry and the synthesis and manufacturing of oligonucleotides, conjugates, and amidites. Shubh earned his PhD from CMU under the mentorship of Prof. Bruce Armitage & Prof. Danith Ly, studying thermodynamics and kinetics of nucleic acid structures and interactions, and completed postdoctoral research with Prof. Marvin Caruthers at CU, Boulder, where he developed novel phosphorus-modified nucleic acid derivatives. He currently advises early-stage companies on advancing diverse oligonucleotide modalities, including siRNAs, di-siRNAs, ASOs, miRNAs, and antibody-oligo conjugates, toward the clinic.