Senior Scientist, Oligonucleotide Chemistry

Job Title: Senior Scientist, Oligonucleotide  Chemistry

Department: Chemistry

Location: We are only considering candidates who can work onsite in San Diego, CA .

About Sirius

Sirius is a clinical stage biotech company developing innovative siRNA therapies for global markets. We are dedicated to discovering and developing new treatment options for cardiovascular and cerebrovascular disease and translating siRNA technology into transformative medicine for the treatment of chronic diseases. Our most advanced products are SRSD107 for the treatment of thromboembolic disorders, SRSD216 for the treatment of hyperlipoproteinemia, and SRSD101 for the treatment of dyslipidemia.

Founded in 2021 by a world-class leadership team and investors, Sirius is dual headquartered in San Diego, where discovery center is located, and Shanghai, where translational medicine and clinical operation center is based. Sirius has raised nearly US$150 million funding to date from top global VC funds such as OrbiMed and Creacion Ventures.

Summary of Position

We are seeking a highly motivated and experienced Senior Scientist, Oligonucleotide Chemistry to join our research team developing next-generation siRNA therapeutics. The successful candidate will have strong expertise in oligonucleotide synthesis and purification and will play a key role in the design, synthesis, characterization, and optimization of siRNA molecules and chemical modification of oligonucleotides.

Responsibilities

Reasonable accommodations may be made to enable individuals with disabilities to perform these essential functions.

• Responsible for the synthesis, purification, and characterization of siRNA and related oligonucleotide molecules.
• Develop and optimize solid-phase oligonucleotide synthesis processes.
• Apply chemical modifications to siRNA molecules to optimize their stability, potency, pharmacokinetics, tissue distribution, and safety.
• Characterize oligonucleotides using analytical techniques including LC-MS, HPLC/UPLC, UV spectroscopy, and related analytical methods.
• Troubleshoot synthesis and purification issues and develop practical solutions to improve yield, purity, reproducibility, and scalability.
• Support technology development in novel siRNA architectures, chemical modification patterns, conjugation methods, and delivery approaches.
• Design and execute experiments independently, analyze experimental data, and communicate conclusions and recommendations to project teams.
• Maintain accurate experimental records and contribute to technical reports, presentations, patent applications, and scientific publications.
• Collaborate cross-functionally to advance programs toward candidate nomination and preclinical development.

Qualification

Required

• Ph.D. in Organic Chemistry, Medicinal Chemistry, Pharmaceutical Chemistry, Biochemistry, or a related field with approximately 3+ years of relevant industry or postdoctoral experience, or equivalent experience.
• Strong hands-on experience with oligonucleotide synthesis and chemistry.
• Demonstrated expertise in solid-phase oligonucleotide synthesis and phosphoramidite chemistry.
• Experience with purification and analytical characterization of oligonucleotides.
• Proficiency with analytical/purification techniques such as HPLC/UPLC, ÄKTA and LC-MS etc.
• Strong knowledge of nucleic acid chemistry and chemical modification of oligonucleotides.
• Ability to work independently on designing experiments, troubleshooting technical challenges, analyzing experimental data, and summarizing key scientific findings and conclusions.
• Strong written and oral communication skills.
• Strong learning agility and ability to rapidly acquire new technical skills.

Preferred

• Experience with bioconjugation of oligonucleotides to other modalities.
• Knowledge of peptide synthesis and modification.
• Demonstrated strong problem-solving skills
• Experience with analytical method development and characterization of oligonucleotide
• Experience working with external CRO/CDMO partners.