Scientist/Sr. Scientist, Oligo Chemistry
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Job Description
Scientist/Sr. Scientist in Oligonucleotide Chemistry leading oligonucleotide discovery programs. Collaborate with cross-functional teams for therapeutic oligonucleotides development.
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, extrahepatic delivery, durability, and safety.
- Maintain thorough technical documentation and effectively communicate experimental strategies, results, and recommendations to cross-functional teams.
Requirements:
- Ph.D. in Organic Chemistry, Medicinal Chemistry, or a related discipline with 0-6 years of relevant industry experience, or M.S. with 2-8 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.
Benefits:
- Target annual bonus
- Equity-based compensation
- Participation in the company’s benefit programs
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