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On-site
Waltham, MA
Posted · 20.09.2026
Greenhouse (US)

# Principal Scientist, Oligonucleotide (PMO, ASO) Development

Dyne Therapeutics

Company Overview: Dyne Therapeutics is focused on delivering functional improvement for people living with genetically driven neuromuscular diseases. We are developing therapeutics that target muscle and the central nervous system (CNS) to address the root cause of disease. The company is advancing clinical programs for Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1) as well as preclinical programs for facioscapulohumeral muscular dystrophy (FSHD), Pompe disease and multiple DMD mutations. At Dyne, we are on a mission to deliver functional improvement for individuals, families and communities. Learn more at&nbsp;https://www.dyne-tx.com/, and follow us on&nbsp;X,&nbsp;LinkedIn&nbsp;and&nbsp;Facebook.Role Summary The Principal Scientist of Oligonucleotide Development will lead the chemical synthesis strategy for PMO and modified ASO payload molecules, managing execution both internally and across CDMOs. This role oversees the early development aspects from preclinical process and analytical development leading into GMP manufacture for IND-enabling studies. This role will ensure the delivery of robust, scalable, and cost-effective manufacturing processes, serve as the primary technical lead for external CDMOs, driving aggressive timelines while delivering well-characterized products optimized for our proprietary bioconjugation platform. The Principal Scientist of Oligonucleotide Development will steer the development of preclinical assets and help define CMC strategies within a matrixed environment. The role will play a critical role in global regulatory filings (IND, IMPD, etc.) by authoring and reviewing key Module 3 sections.&nbsp; This role is based in Waltham, MA without the possibility of being a remote role. Physical presence onsite is expected on 4-5 days/week. Key Responsibilities Technical Leadership &amp; Strategy Drive Process Excellence:&nbsp;Lead the design, optimization, and execution of process development for PMO and modified ASO payload molecules, ensuring scalability for clinical supply. Define Analytical Strategy:&nbsp;Support analytical development, focusing on robust impurity control strategies, raw material specifications, and comprehensive physicochemical characterization for both oligonucleotide payloads and conjugated protein drug substances. Innovate &amp; Improve:&nbsp;Proactively identify and implement emerging technologies and continuous improvement initiatives to enhance product quality and manufacturing efficiency. Prepare technical source documents, publications, and oral presentations Prepare and review relevant CMC and product related sections and documentation for regulatory submission (IND, IMPD etc.) Review and approve documents related to development and cGMP operations, including Tech Transfer, Process Characterization, Master Batch Records (MBRs) and Campaign Summary Reports External Partner &amp; Project Management Technology Transfer:&nbsp;Spearhead the seamless transfer of processes and analytical assays to external partners, ensuring technical success and data integrity. Issue Resolution:&nbsp;Serve as the technical lead for resolving complex manufacturing or analytical challenges, driving timely and data-driven solutions. Regulatory &amp; Quality Compliance Regulatory Authoring:&nbsp;Contribute to regulatory filings (IND, IMPD, etc.), ensuring high-quality, submission-ready Module 3 content. GMP Oversight:&nbsp;Review and approve critical development and cGMP documentation, including Tech Transfer protocols, Master Batch Records (MBRs), and Campaign Summary Reports. Knowledge Dissemination:&nbsp;Oversee the creation of technical source documents, publications, and high-level presentations for internal stakeholders and external forums. Education &amp; Experience Bachelor’s degree in Biochemistry, Chemical Engineering, Chemistry, or Pharmaceutical Sciences 8+ years of relevant pharmaceutical/biotech industry experience (advanced degree preferred) Oligonucleotide Expertise:&nbsp;Proven track record in the process chemistry and development of&nbsp;PMO and modified ASO oligonucleotides, including deep technical knowledge of synthesis and purification. Experience in Research &amp; Development preferably in a clinical-stage biotechnology company External Management:&nbsp;Direct experience in the oversight of&nbsp;CDMOs, including managing technology transfers. Analytical Depth:&nbsp;Technical proficiency in analytical development, including impurity control strategies and physicochemical characterization of payload and conjugated drug substances. Strategic Problem Solving:&nbsp;Ability to navigate shifting priorities and evolving timelines using robust analytical and risk-mitigation capabilities. Collaborative Influence:&nbsp;Exceptional interpersonal and communication skills, with a proven ability to lead and influence cross-functional teams, contractors, and third-party vendors. &nbsp; #LI-OnsiteMA Pay Range$159,000&mdash;$200,000 USD&nbsp; The pay range reflects the base pay range Dyne reasonably expects to pay for this role at the time of posting. Individual compensation depends on factors such as education, experience, job-related knowledge, and demonstrated skills. The statements contained herein reflect general details as necessary to describe the principles functions for this job, the level of knowledge and skill typically required, and the scope of responsibility, but should not be considered an all-inclusive listing of work requirements.&nbsp; Individuals may perform other duties as assigned, including work in other functional areas to cover absences or relief, to equalize peak work periods or otherwise balance workload. Dyne Therapeutics is an equal opportunity employer and will not discriminate against any employee or applicant on the basis of age, color, disability, gender, national origin, race, religion, sexual orientation, veteran status, or any classification protected by federal, state, or local law.

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