Scientist II – Oligonucleotide Process Development, Manufacturing Development and Scale-Up
$85,600–$156,000 year
On-siteSan Diego, California, United States
Job Summary
Execute solid-phase oligonucleotide syntheses on automated synthesizers using phosphonamidite chemistry, optimizing cycles for coupling, capping, and oxidation steps. Drive scale-up from nano-gram process development to micro/milli-gram batches, selecting solid supports and columns while synthesizing complex modified sequences like phosphorothioates and LNA. Characterize crude and purified products via analytical UPLC, IEX-HPLC, and LC/MS to identify impurities, then troubleshoot failures and implement process improvements. Author technical documents including protocols, batch records, and tech-transfer packages while partnering cross-functionally with Analytical, Quality, and Manufacturing teams. Maintain a compliant lab environment adhering to cGMP and ICH guidelines.
Required Qualifications
- Hands-on experience with solid-phase oligonucleotide synthesis using phosphonamidite chemistry
- B.S in biological or physical sciences, or mathematics; with minimum of 4 yrs
- M.S. w/ minimum 2 yrs experience
- Or Ph.D.
- Direct experience operating at least one automated oligonucleotide synthesizer
- Working knowledge of common solid supports (CPG, polystyrene, UnyLinker) and the relationship between support loading, column geometry, and synthesis scale
- Hands-on experience with LC/MS for oligonucleotide characterization, with demonstrated ability to identify and quantify related impurities (n−1, n+1, depurination, longmers, branched species, oxidation/desulfurization products) and to perform sequence confirmation by MS/MS fragmentation
- Familiarity with complementary oligonucleotide analytical techniques: UPLC/HPLC (RP and IEX) for purity assessment
- Strong scientific writing and documentation skills
- Ability to work independently, prioritize multiple projects, and meet deadlines in a fast-paced environment
Desired Qualifications
- Experience in a GMP or pharmaceutical API manufacturing environment
- Experience operating Waters LC/MS systems (e.g., Xevo, SYNAPT, ACQUITY-MS) and associated data-processing software (MassLynx, UNIFI)
- Experience with scale-up (nmol to mmol scale) and tech transfer of oligonucleotide processes
- Familiarity with conjugated oligonucleotides (e.g., lipid conjugates)
- Experience with downstream operations — cleavage/deprotection, IEX or RP preparative purification, ultrafiltration/diafiltration, and lyophilization
- Familiarity with statistical tools (JMP, Minitab) and Design of Experiments (DoE)
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