Principal Scientist, Oligonucleotide Chemistry

About Stoke

Stoke Therapeutics (Nasdaq: STOK) is a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine. Using Stoke’s proprietary approach, the company is developing antisense oligonucleotides (ASOs) to selectively restore naturally occurring protein levels. Stoke’s first medicine in development, zorevunersen, has demonstrated the potential for disease modification in patients with Dravet syndrome and is currently being evaluated in a Phase 3 study.

Stoke entered into a strategic collaboration with Biogen in 2025 to develop and commercialize zorevunersen for Dravet syndrome. Under the collaboration, Stoke retains exclusive rights for zorevunersen in the United States, Canada, and Mexico;
Biogen receives exclusive rest of world commercialization rights

We are seeking a dedicated and highly motivated Principal Scientist in Oligonucleotide chemistry to join a dynamic team focused on advancing oligonucleotide-based therapeutics. Within the chemistry team, you will work with talented scientists in managing the synthesis of bioactive oligonucleotides for our drug discovery programs and delivering to the project teams with strict timelines. Successful candidates will have significant experience with solid phase chemical synthesis of oligonucleotide, conjugation, HPLC purification, and LC-MS analysis.

This position will report to the Director, Chemistry.

• Independently design and implement scientific and synthesis strategies relating to the research and development of antisense and other synthetic oligonucleotide therapeutics.
• Contribute to multiple projects and provide key technical knowledge to the project team.
• Plan and execute solid-phase oligonucleotide synthesis for SAR campaigns on several projects.
• Participate in the identification, development, validation and implementation of both current and next-generation technologies to enable proprietary ASO therapeutic development including purchase and installation of hardware and software supporting synthesis, purification, and characterization of oligonucleotides.
• Demonstrate working knowledge of conjugation chemistry and techniques aimed at producing novel conjugates.
• Demonstrates understanding of the chemistry of nucleosides, nucleotides, and oligonucleotides as applied to antisense and other oligonucleotide technologies.
• Stay current with scientific literature and understanding of the state of the art in oligonucleotide chemistry, purification, and screening strategies.
• Work with both internal chemistry team and external CRO’s to generate innovative solutions to synthetic and drug design challenges within the context of oligonucleotide drug discovery projects.
• Authors reports and manuscripts. May contribute to patent filings and/or regulatory filing.

• PhD in Oligonucleotide Chemistry and relevant experience in a drug discovery environment with at least 8 years of oligonucleotide synthesis experience in a drug discovery environment, Master’s degree with 12+ years of experience or Bachelor’s degree with 18+ years of experience.
• Strong practical knowledge of design, synthesis, and purification of synthetic oligonucleotides.
• Experience in scale-up synthesis would be a plus.
• Excellent project/time management, and problem-solving skills.
• Excellent written and verbal communication skills, including making effective and compelling presentations in both large and small groups and communicating complex scientific and nonscientific issues to program teams.
• Strong people skills and the ability to thrive in a team and goal driven environment
• Experience designing, synthesizing and purifying oligonucleotides to support research and scale up studies.
• Proven track record of scientific contributions in oligonucleotide and conjugates research as evidenced by publications/presentations/patent applications and/or the identification of preclinical development candidates.

Stoke operates in Bedford, MA. This is a lab-based position based in our Bedford, MA location.

This position will require approximately 0% travel.

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