Senior Scientist, Organic, Medicinal, and Oligonucleotide Chemistry

Sirius Therapeutics, Inc.; San Diego (CA); On-site; USD 120,000 - 180,000; Full time

Job summary

Sirius Therapeutics, Inc. in San Diego, CA, is seeking a Senior Scientist for Organic, Medicinal, and Oligonucleotide Chemistry to advance siRNA therapeutic programs.

You will design and synthesize modified nucleosides, phosphoramidites, linkers, and ligands, and integrate them into siRNA and related oligonucleotides for preclinical development. The role requires a PhD in a relevant chemistry field and hands-on expertise in synthetic organic chemistry, bioconjugation, and oligonucleotide

Qualifications

• PhD in organic, medicinal, pharmaceutical chemistry or related field with 3+ years of industry or postdoc experience.
• Strong hands-on expertise in synthetic organic chemistry and bioconjugation.
• Experience in building blocks for oligonucleotide modification or conjugation (modified nucleosides, phosphoramidites, linkers, conjugation handles).
• Understanding of oligonucleotide chemical modifications and their impact on nuclease stability, potency, PK, and safety.

Responsibilities

• Design and synthesize building blocks for novel oligonucleotide modifications (modified nucleosides, phosphoramidites, reagents for backbone modification).
• Design and synthesize lipids, targeting ligands, linkers, and conjugation handles.
• Incorporate modifications into siRNA and related oligonucleotides and assess nuclease stability, potency, pharmacokinetics, and safety.
• Synthesize, purify, and characterize siRNA and related oligonucleotides for discovery and preclinical development.
• Develop and optimize workflows for solid-phase oligonucleotide synthesis, bioconjugation, and purification; develop analytical methods (LC–MS, HPLC/UPLC, UV).
• Establish SAR for ligand-oligonucleotide conjugates; optimize ligand, linker, and conjugation to improve delivery.
• Contribute to platform development by exploring novel siRNA architectures and delivery approaches.
• Independently design experiments, troubleshoot, analyze data, and communicate findings to project teams.
• Maintain accurate records and contribute to reports, publications, and patent applications.
• Collaborate with cross-functional teams to advance programs toward candidate nomination.

Skills

Synthetic organic chemistry

Bioconjugation

Oligonucleotide modification

Analytical characterization

Independent experiment design

Education

PhD in organic/medicinal/pharmaceutical chemistry or related

Tools

Automated solid-phase oligonucleotide synthesis

Oligonucleotide bioconjugation

LC-MS

HPLC/UPLC

Job description

Job Title: Senior Scientist, Organic, Medicinal, and Oligonucleotide Chemistry

Reporting to: Associate Director, Chemistry

Location: San Diego, CA [Relocation not offered]

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 chronic disease. 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 headquartered in San Diego, where the 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 Senior Scientist to join our research team developing next‑generation siRNA therapeutics. This is a hands‑on role for an organic or medicinal chemist with expertise in synthetic organic chemistry and bioconjugation and a strong understanding of oligonucleotide chemistry. The successful candidate will design and synthesize modified nucleosides, phosphoramidites, linkers, and targeting ligands, then incorporate them into siRNA and related oligonucleotides. This work will support drug discovery programs and the technology development for extrahepatic tissue‑specific delivery.

Responsibilities

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

• Design and synthesize building blocks for novel oligonucleotide modifications, including modified nucleosides, phosphoramidites, and reagents for backbone modification.
• Design and synthesize lipids, targeting ligands, functional linkers, and conjugation handles.
• Incorporate novel modifications into siRNA and related oligonucleotides. Evaluate how these changes affect nuclease stability, potency, pharmacokinetics, and safety.
• Synthesize, purify, and characterize siRNA and related oligonucleotides in support of discovery and preclinical development programs.
• Develop and optimize workflows for solid‑phase oligonucleotide synthesis, bioconjugation, and purification. Develop analytical methods for product characterization and impurity profiling using LC–MS, HPLC/UPLC, UV spectroscopy, and related techniques.
• Establish structure–activity relationships for ligand–oligonucleotide conjugates. Optimize ligand, linker, and conjugation chemistry to improve delivery to target tissues.
• Contribute to platform development by exploring novel siRNA architectures, chemical modification patterns, conjugation strategies, and delivery approaches.
• Independently design and execute experiments, troubleshoot technical challenges, analyze data, and communicate findings and recommendations to project teams.
• Maintain accurate experimental records and contribute to technical reports, presentations, patent applications, and scientific publications.
• Collaborate with cross-functional teams to advance programs toward candidate nomination and preclinical development.

Qualifications

Required

• Ph.D. in organic chemistry, medicinal chemistry, pharmaceutical chemistry, or a related field, with three or more years of relevant industry or postdoctoral experience, or equivalent experience.
• Strong hands‑on expertise in synthetic organic chemistry and bioconjugation.
• Experience in designing and synthesizing building blocks for oligonucleotide modification or conjugation, such as modified nucleosides, phosphoramidites, functional linkers, or conjugation handles.
• Understanding of oligonucleotide chemical modifications and how they influence nuclease stability, potency, pharmacokinetics, and safety.
• Proficiency in chromatographic purification and analytical techniques, including NMR, HPLC/UPLC and LC–MS.
• Ability to design experiments independently, solve technical problems, interpret data, and communicate conclusions clearly in writing and in presentations.
• Ability to learn and apply new experimental techniques quickly.

Preferred

• Hands‑on experience with automated solid‑phase oligonucleotide synthesis, oligonucleotide bioconjugation, purification, and analytical characterization.
• Experience with peptide synthesis and modification.
• Experience working with external CRO or CDMO partners.