Scientist, Oligo Chemistry

Korsana Biosciences•Waltham, MA

3d•$115,000 - $140,000

About The Position

We are seeking a highly motivated Scientist in Oligonucleotide Chemistry to lead the design, optimization, and characterization of next-generation therapeutic oligonucleotides. Working closely with cross-functional teams spanning bioinformatics, biology, pharmacology, formulation, and delivery sciences, this individual will drive oligonucleotide discovery programs from target identification through candidate selection. The successful candidate will have deep expertise in organic synthesis, nucleoside and phosphoramidite chemistry, and therapeutic oligonucleotide design, with a strong understanding of the chemical principles governing siRNAs, antisense oligonucleotides (ASOs), PMOs, and other emerging RNA-targeting modalities. They will develop medicinal chemistry strategies that leverage state-of-the-art chemical modifications and oligonucleotide architectures to optimize potency, stability, tissue distribution, durability, and safety, while providing scientific leadership for both internal research and external CRO activities.

Requirements

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.
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 the ability to present complex scientific concepts to multidisciplinary teams.
Demonstrated ability to work independently while thriving in a collaborative, fast-paced, and highly interdisciplinary research environment.
Passion for advancing transformative nucleic acid medicines through innovative chemistry and rigorous scientific execution.

Nice To Haves

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.

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.