Scientist, Oligo Chemistry

Responsibilities

• Design and optimize chemically modified oligonucleotides, including siRNAs, ASOs, PMOs, and other emerging modalities.
• Develop novel nucleoside analogs, phosphoramidites, backbone chemistries, and oligonucleotide architectures to improve potency, stability, durability, and tissue delivery.
• Generate and interpret structure-activity relationships (SAR) to guide lead optimization across oligonucleotide chemistries and modification patterns.
• Design oligonucleotide libraries in collaboration with bioinformatics and biology teams to support cellular and in vivo screening campaigns.
• Develop synthetic routes for novel oligonucleotide building blocks using modern organic and nucleoside chemistry approaches.
• Oversee the synthesis, purification, and analytical characterization of oligonucleotides and intermediates, leveraging both internal capabilities and external CRO partners.
• Manage external CROs, including experimental design, prioritization, technical oversight, data review, timeline management, and troubleshooting to ensure high‑quality and timely project execution.
• Develop and apply analytical methods, including RP‑HPLC, IEX, LC‑MS, CE, and SEC, to characterize oligonucleotides and support process development.
• Partner closely with biology, pharmacology, toxicology, and translational sciences teams to understand how chemical modifications impact biological activity and therapeutic performance.
• Contribute to next‑generation oligonucleotide platform technologies, including novel chemistries, delivery strategies, and manufacturability improvements.
• Evaluate emerging technologies and scientific literature to identify innovative approaches that enhance potency, extra‑hepatic delivery, durability, and safety.
• Maintain thorough technical documentation and effectively communicate experimental strategies, results, and recommendations to cross‑functional teams.

• Ph.D. in Organic Chemistry, Medicinal Chemistry, or a related discipline with 0‑3 years of relevant industry experience, or M.S. with 2‑5 years of industry experience in oligonucleotide therapeutic development.
• Extensive hands‑on experience in organic synthesis and nucleoside chemistry, including the synthesis and characterization of phosphoramidites or related oligonucleotide building blocks.
• Demonstrated expertise in therapeutic oligonucleotide chemistry, including siRNA, antisense oligonucleotides, splice‑switching oligonucleotides, PMOs, or related modalities.
• Possess a deep understanding of contemporary oligonucleotide modification patterns, including 2′-O‑methyl, 2′-fluoro, LNA, cEt, constrained analogs, phosphorothioate stereochemistry, phosphodiester incorporation, glycol nucleic acids, morpholino chemistry, and other emerging chemistries and how individual modifications influence potency, nuclease resistance, pharmacokinetics, biodistribution, immunostimulation, and toxicity.
• Direct experience with oligonucleotide synthesis platforms and purification workflows, including automated solid‑phase synthesis and preparative HPLC.
• Strong analytical expertise with LC‑MS, RP‑HPLC, ion exchange chromatography, capillary electrophoresis, MALDI‑TOF, and related characterization techniques.
• Experience designing and interpreting medicinal chemistry SAR campaigns for oligonucleotide therapeutics.
• Familiarity with oligonucleotide delivery technologies, including GalNAc conjugates, lipid conjugates, peptide conjugates, antibody‑oligonucleotide conjugates, nanoparticles, or other targeted delivery systems is desirable.
• Experience supporting lead optimization and candidate selection within a drug discovery environment is preferred.

• Exceptional scientific creativity and problem‑solving skills with the ability to design innovative chemical solutions to challenging therapeutic problems.
• Deep understanding of the evolving oligonucleotide therapeutics landscape and current state‑of‑the‑art chemistry across siRNA, ASO, PMO, and emerging RNA‑targeting platforms.
• Ability to integrate medicinal chemistry, synthetic chemistry, biology, and pharmacology data into coherent lead optimization strategies.
• Strong communication skills with…