Principal Scientist​/Associate Director, Downstream Process Development Formulation

Job Title:

Principal Scientist/Associate Director, Downstream Process Development Formulation

Location:

San Diego

Job Type: Full-Time

About Us:

A new stealth-mode biotech focused on in vivo gene editing.

Job Summary:

We are seeking an experienced Principal Scientist/Associate Director to lead downstream process development for our targeted lipid nanoparticle (tLNP) platform. This is a hands‑on, lab‑based role focused on the purification, concentration, and buffer exchange of tLNP drug product using size exclusion chromatography (SEC), tangential flow filtration (TFF), and complementary downstream unit operations. The successful candidate will be a technical expert in nanoparticle purification, responsible for developing robust, scalable downstream processes that deliver high‑purity tLNP product while preserving particle integrity, targeting functionality, and cargo activity.

This individual will also contribute to formulation development, stability assessment, and technology transfer to CDMOs. Title and salary commensurate with experience.

• Design, optimize, and execute downstream purification processes for targeted LNPs, with emphasis on SEC (gravity flow and column chromatography, including CIMmultus monolithic columns) and TFF (hollow fiber and flat sheet cassettes) at research and pilot scale.
• Develop and optimize TFF operating parameters including transmembrane pressure, cross-flow rate, membrane molecular weight cutoff selection, diafiltration volumes, and flux decay management to maximize product recovery and minimize particle stress.
• Establish SEC-based purification methods to separate assembled tLNP product from free protein, unincorporated lipid components, and process‑related impurities; optimize resin selection, column loading, and elution conditions.
• Characterize downstream process intermediates and final drug product using DLS, zeta potential, nanoparticle tracking analysis (NTA), cryo‑TEM, encapsulation efficiency assays, and protein/lipid quantitation methods.
• Evaluate and benchmark alternative and emerging purification modalities (e.g., bind‑elute chromatography, membrane chromatography, depth filtration) for tLNP applications.
• Develop and optimize final formulation and buffer exchange conditions to ensure tLNP stability, including excipient screening, cryoprotectant selection, and lyophilization feasibility assessment.
• Lead process characterization studies to define critical process parameters (CPPs) and critical quality attributes (CQAs) for downstream unit operations.
• Support technology transfer of downstream processes to CDMOs, including process documentation (batch records, SOPs, technical reports), on‑site support, and process troubleshooting.
• Collaborate with formulation scientists, analytical scientists, and biology teams to ensure downstream processes preserve LNP integrity, targeting ligand functionality, and cargo bioactivity.
• Design and execute process development studies using DOE approaches to systematically optimize purification and formulation parameters.
• Maintain detailed electronic laboratory notebooks and contribute to regulatory filings (IND/CTA) for downstream process and drug product CMC sections.
• Stay current with advances in nanoparticle purification, LNP downstream processing, and scalable manufacturing technologies.

• D. in Chemical Engineering, Biomedical Engineering, Pharmaceutics, Chemistry, Biochemistry, or a related field with 5+ years of industry experience; or M.S. with 8+ years of relevant industry experience, or B.S. with 10+ years of relevant experience.
• Demonstrated hands‑on expertise in TFF process development for nanoparticle or biopharmaceutical applications, including membrane selection, process optimization, and…