Oligonucleotide therapeutics are moving beyond a narrow set of established chemistries and hepatic targets toward a rapidly diversifying landscape. New phosphorus chemistries and 2' substituent modifications are being exploited to tune charge, functionality, and activity while avoiding innate immune sensors, and conjugation strategies spanning small molecule ligands, peptides, lipids, and antibodies are extending activity to new tissues. Realizing this potential depends on the interplay between molecular structure, rational design, and targeted delivery, each of which introduces new chemical, analytical, and regulatory demands.
Nucleic Acid Insights has assembled a panel of experts spanning synthetic chemistry, therapeutic development, and CMC to examine how progress across structure, design, and targeting is extending the reach of oligonucleotide medicines.
The panel will examine how novel modifications and conjugation chemistries shape synthesis routes, supply chains, and cost of goods; and how the field should address the compounding analytical, physicochemical, and regulatory challenges of characterizing conjugates and antibody-oligonucleotide conjugates (AOCs) as single entities.
Learning points:
- Examine how new phosphorus chemistries and 2' substituent modifications can be used to alter oligonucleotide charge, functionality, and activity while avoiding innate immune sensors
- Understand how conjugation strategy choices between small molecule ligands, peptides, lipids, and antibodies shape synthesis routes, raw material supply chains, and long-term cost of goods
- Explore the compounding analytical and physicochemical challenges of characterizing peptide conjugates and AOCs as single entities, and the design decisions that ease or complicate them
Jonathan Neidigh, PhD
Independent Consultant
Jonathan W. Neidigh is a consultant providing CMC services for pharmaceutical and biotechnology companies to help solve technical challenges from discovery research through clinical phase development for complicated drugs. He earned his PhD in organic chemistry from the University of Washington where he characterized the first approved GLP-1 drug, Exendin-4, and designed a miniature protein. He conducted research in DNA Damage and Repair as well as biomarkers of inflammation while teaching graduate and medical students as a biochemistry professor for 15 years before transition into the pharmaceutical industry where he worked for 10 years at CDMOs. Jonathan’s experience includes analytical, bioanalytical, formulation, and process development for complex drugs that combine nucleic acids with lipids or proteins.
Praveen Kumar Pogula, PhD
Director at Quralis
Praveen Pogula, PhD, is a Director at Quralis, where he supports research and development, CMC strategy, and manufacturing activities for antisense oligonucleotide therapeutics targeting central nervous system disorders. He is a nucleic acid chemist with more than 20 years of experience spanning ASOs, siRNA, mRNA, RNA editing, nucleoside chemistry, oligonucleotide conjugation, targeted delivery, and lipid nanoparticles. His expertise includes oligonucleotide design and synthesis, process development, purification, analytical characterization, formulation, technology transfer, and external manufacturing oversight. Throughout his career, he has led multidisciplinary scientific teams and collaborated with contract research and manufacturing organizations to advance nucleic acid therapeutics from discovery through development. He holds a PhD in Medicinal Chemistry and is an inventor and author on multiple patents and peer-reviewed scientific publications.
Sayantan Chatterjee, PhD
Scientist in Medicinal Chemistry at Korro Bio
Dr Sayantan Chatterjee is a nucleic acid chemist whose research integrates synthetic organic chemistry, RNA chemical biology, and therapeutic oligonucleotide development. He earned his PhD in Chemistry from Stanford University under the mentorship of Prof. Eric T. Kool, where he developed reagents for selective RNA chemical modification and structure analysis. He has designed RNA-reactive small molecules, phosphoramidites, and modified oligonucleotides that advance RNA therapeutics. Currently a Scientist in Medicinal Chemistry at Korro Bio, he develops novel chemistries for ADAR-mediated mRNA editing. His work has led to multiple patents, commercialized molecules, and publications in leading chemistry journals.
Derek O'Flaherty, PhD
Associate Chair at University of Guelph
Derek O’Flaherty received his Honours BSc in Chemistry with a Minor in Multidisciplinary Sciences from Concordia University (Montreal, Canada), where he remained for a PhD in the laboratory of Christopher Wilds. After a postdoctoral fellowship in Jack Szsotak’s laboratory at Massachusetts General Hospital/Harvard University, and working as a Scientist at Alnylam Pharmaceuticals, he joined the Department of Chemistry at the University of Guelph as an Assistant Professor in 2020. He was promoted to Associate Professor in 2026, and currently serves as Associate Chair of the Department of Chemistry. His research integrates nucleic acid chemistry, biotechnology, and origins-of-life chemistry, with a focus on developing chemical methods for oligonucleotide synthesis, bioconjugation, nonenzymatic genome replication, and synthetic cell assembly.
Jokubas Leikauskas
Commissioning Editor at Nucleic Acid Insights
