Senior Scientist, Oligonucleotide Chemistry

Role Summary

The Senior Scientist in Oligonucleotide Chemistry will be focusing on the design, development, and implementation of chemically modified oligonucleotides, including siRNA, ASO, and emerging next-generation modalities, to support both in vitro and in vivo studies. This role will also oversee external CRO partners responsible for oligonucleotide synthesis and quality control, manage and maintain the oligonucleotide database, and drive innovation in novel chemistries, including advanced modifications and diverse siRNA formats.

In addition to chemical modification strategy, this role is expected to take an active role in siRNA sequence design, working closely with internal bioinformatics resources while contributing chemistry-informed design insights. The position will be responsible for end-to-end design optimization, integrating both sequence and chemical modification considerations to improve efficacy, stability, and developability.

The role will also contribute to the maintenance and continuous improvement of internal oligonucleotide design tools and databases, requiring familiarity with oligo-design systems and the ability to support or coordinate their optimization.

Additionally, this role will collaborate with the intellectual property team to support invention disclosures and patent filings for novel chemistry and design strategies.

Key Responsibilities

• Lead the integrated design of oligonucleotides, combining sequence design and chemical modification strategies to optimize potency, specificity, and stability
• Develop and apply computational and data-driven approaches to guide oligonucleotide design, including sequence selection, off-target minimization, and structure-function optimization
• Work at the interface of chemistry and bioinformatics to translate sequence-level insights into chemistry-informed design decisions
• Oversee external CROs for oligonucleotide synthesis and QC, including scope definition, timeline management, troubleshooting, and data review
• Own and maintain the oligonucleotide database, ensuring high-quality data integration across sequence, modification, QC, and biological performance
• Drive innovation in next-generation oligonucleotide chemistries and formats, including conjugates, bispecific siRNA, and delivery-enabling designs
• Continuously improving internal oligonucleotide design platforms, including sequence design pipelines, modification annotation systems, and data tracking infrastructure
• Collaborate with bioinformatics and software teams to develop, refine, or implement design algorithms and tools for next-generation oligonucleotide modalities
• Analyze and interpret experimental and analytical data (e.g., HPLC, LC-MS, in vitro/in vivo data) to iteratively refine design hypotheses and models
• Partner with cross-functional teams (biology, DMPK, bioinformatics, and program leadership) to ensure effective translation from design to biological outcomes
• Support IP strategy by contributing to invention disclosures and patent filings covering both design methodologies and chemical innovations
• Identify opportunities to improve design efficiency, scalability, and data utilization through automation and digital tools

Qualifications

Required

• PhD in Chemistry, Chemical Biology, Bioinformatics, or related field with relevant experience; or BS/MS with extensive experience in oligonucleotide design and chemistry
• Strong expertise in chemically modified oligonucleotides (siRNA/ASO), including synthesis, structure, and SAR
• Ability to integrate sequence design with chemical modification strategies to drive functional outcomes
• Familiarity with oligonucleotide design tools, databases, and computational workflows, with the ability to support or improve them
• Experience working with CROs and delivering oligonucleotide materials to support discovery programs
• Strong analytical thinking and ability to interpret multi-dimensional datasets
• Excellent cross-functional communication skills

Preferred

• Exposure to multi-modal oligonucleotide design, such as conjugates (GalNAc, lipid), bispecific constructs, or delivery-enhancing chemistries
• Experience with automation or high-throughput design workflows
• Demonstrated experience in siRNA/ASO sequence design, including use of design algorithms, rulesets, or predictive models
• Experience with off-target prediction tools, RNA structure modeling
• Prior experience contributing to design platform development or digital transformation initiatives
• Programming or scripting skills (e.g., Python) for data analysis, pipeline development, or tool integration
• Track record of innovation demonstrated through publications, patents, or platform development