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. Stoke 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

Stoke’s initial focus for its TANGO platform is on diseases of the central nervous system and the eye that are caused by a loss of ~50% of normal protein levels (haploinsufficiency).

Stoke has identified STK-002 as a clinical candidate for the potential treatment of autosomal dominant optic atrophy (ADOA), the most common inherited optic nerve disorder. The company is also pursuing a potential new medicine for Syngap1, a severe and rare neurodevelopmental disorder, in collaboration with Acadia Pharmaceuticals.

Proof of concept has been demonstrated in other organs, tissues, and systems, supporting broad potential for the Company’s proprietary approach.

Position Purpose:

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.

Key Responsibilities:

• 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.
  
  

Required Skills & Experience:

• 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.
  
  

Location(s):

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

Travel:

This position will require approximately 0% travel.

Culture & Values:

At Stoke, we believe that innovation, the ability to successfully advance our ground-breaking science and having fun as a team are enhanced by being together in person, at least periodically. We allow for flexibility in work arrangements that balance individual’s needs and preferences with the needs of our business and our desire to foster a culture of collaboration and innovation.

Our values guide our work to deliver meaningful medicines for people who need them. We are committed to being true to ourselves, to our colleagues, and to the people with severe diseases who are counting on us. We embrace diversity within a unique culture that is defined by our values. Our employee-led Diversity, Inclusion, and Belonging Committee (DIB) underscores the importance of DIB to who we are and what we do.

Benefits & Compensation:

At Stoke Therapeutics we are proud to offer comprehensive and competitive employee benefits, including medical, dental and vision insurance; life, long and short-term disability insurance; Paid Parental Leave; a 401K program with company match, unlimited vacation time, and an Employee Stock Purchase Program (ESPP). Compensation is market competitive for the industry and directly commensurate with experience. All positions are bonus and stock eligible.

Interested candidates: Please visit Stoke’s website to learn more and apply directly to the position listed on our Career Center.

For more information, visit stoketherapeutics.com or follow the company on X at @StokeTx.

All applicants will receive consideration for employment without regard to race, color, age, religion, sex, sexual orientation, gender identity, national origin, physical or mental disability or protected veteran status.

Stoke participates in E-Verify.