Scientist II, mRNA Research & Production

Profluent is an AI-first protein design company. Founded in 2022, we develop deep generative models to design and validate novel, functional proteins to revolutionize biomedicine. Based in Emeryville, CA, we are backed by leading investors including Altimeter Capital, Bezos Expeditions, Spark Capital, Insight Partners, Air Street Capital, AIX Ventures, and Convergent Ventures, and have raised over $150M to date. Profluent is seeking a highly motivated Scientist II to drive mRNA production and process development for our customized base editor programs. This is a hands-on, lab-based role focused on the synthesis, purification, characterization, and optimization of research-grade mRNA for high-throughput screening, cell-based assays, and scaled production for mouse studies. This individual will serve as the technical lead for Profluent’s internal mRNA production core function, bridging molecular design and high-quality material generation for in vitro and in vivo studies. The successful candidate will bring strong experience with IVT-based mRNA production, template preparation, purification, analytics, troubleshooting, and workflow optimization, as well as the ability to coordinate and mentor a small team executing routine production and analytical workflows. The role will initially focus on customized base editor mRNAs and will expand over time to support additional programmable genome engineering modalities, including engineered recombinases and other RNA-delivered therapeutic systems. Responsibilities Lead and execute end-to-end research-grade automated mRNA production workflows, including template preparation, plasmid DNA sequencing data analysis, linearization, IVT, capping or cap analog workflows, nucleotide modification, purification, buffer exchange, storage, and batch release for research use Design mRNA (5’/3’ UTR, coding sequence, modifications, etc.) to improve protein yield, activity, and specificity using established and cutting-edge methodology Manage and mentor a small mRNA production core function, helping coordinate production schedules, train team members, review batch quality, and maintain reliable material delivery to R&D teams Partner with payload engineering, delivery, in vivo pharmacology, bioanalytics, and translational teams to ensure mRNA materials are fit-for-purpose for platform and program needs Produce high-quality mRNA for rapid screening of customized base editors in cell-based assays, as well as scaled batches to support mouse studies, assay development, and early translational experiments Improve IVT and purification workflows to increase yield, purity, consistency, turnaround time, and functional performance while minimizing impurities such as dsRNA, abortive transcripts, truncated products, residual template DNA, endotoxin, and other process-related contaminants Implement and interpret fit-for-purpose mRNA analytical assays, including concentration, integrity, transcript purity, size distribution, dsRNA, residual DNA, endotoxin, and functional expression or potency readouts Use analytical platforms such as Fragment Analyzer, TapeStation, Bioanalyzer, gel or capillary electrophoresis, HPLC/UPLC, dsRNA ELISA, endotoxin assays, qPCR/ddPCR, and cell-based assays to characterize mRNA quality Engage and coordinate CROs for production and analytics Maintain clear SOPs, batch records, analytical summaries, sample inventories, and production documentation to support reliable material handoff and reproducible workflows Analyze production and analytical data to troubleshoot batch failures, identify process trends, and recommend improvements to quality, speed, and robustness Support mRNA production workflows for emerging programmable genome engineering modalities, including engineered recombinases, as Profluent’s platform and portfolio evolve Qualifications PhD, MS, or BS in molecular biology, biochemistry, chemical engineering, bioengineering, biotechnology, pharmaceutical sciences, or a related discipline, with relevant industry experience in mRNA production, RNA process development, nucleic acid manufacturing, or related areas PhD with 2-3 years relevant experience, MS with 10+ years, or BS with 12+ years of relevant experience Deep hands-on experience with IVT-based mRNA production and the technical challenges of generating high-quality RNA for in vitro and in vivo studies Experience with plasmid or DNA template preparation, linearization, IVT, capping or cap analog workflows, nucleotide modification, mRNA purification, and product characterization Strong understanding of mRNA quality attributes, process-related impurities, IVT performance, purification strategies, stability, storage, and the relationship between mRNA quality and biological performance Experience producing mRNA for discovery-stage screening and scaling for in vivo preclinical rodent studies Experience with modified nucleotides, cap analogs, enzymatic capping, polyA strategies, UTR/codon/design-variable screening, or RNA design-for-potency and manufacturability Experience coordinating, training, mentoring, or managing research associates or technical team members in a production, process development, core-lab, or high-throughput R&D environment Experience with preparative chromatography, TFF, bead-based purification, buffer exchange, or other mRNA purification approaches Strong technical judgment, attention to detail, and ability to independently troubleshoot production and analytical workflows Excellent organizational and communication skills, including experience maintaining SOPs, batch records, analytical summaries, and clear technical documentation Ability to work effectively with cross-functional teams in a fast-paced R&D environment Preferences Experience supporting genome editing, base editing, gene writing, engineered recombinases, mRNA/LNP therapeutics, RNA medicines, gene therapy, cell therapy, or other advanced therapeutic modalities Experience with automation-compatible workflows, including deep-well plates, magnetic bead cleanup, KingFisher instruments, liquid handlers, or LIMS-like sample tracking systems Familiarity with LNP formulation interfaces, RNA buffer compatibility, freeze-thaw considerations, storage stability, and downstream delivery-performance impacts Familiarity with GMP readiness, IND-enabling supply strategy, raw material strategy, plasmid supply, enzyme/cap/nucleotide sourcing, quality systems, or CMC planning for RNA therapeutics What We Offer High-growth opportunity with meaningful impact on the future of protein design Competitive compensation package with equity participation 401(k) with a strong employer match Generous PTO policy and commitment to work-life balance Professional development opportunities in a cutting-edge field at the intersection of AI and biology Profluent Bio, Inc is an equal opportunity employer promoting diversity and inclusion in the workspace. We do not discriminate on the basis of race, color, religion, marital status, age, national origin, ancestry, physical or mental disability, medical conditions, veteran status, sexual orientation, gender (including gender identity and gender expression), sex (which includes pregnancy, childbirth, and breastfeeding), genetic information, taking or requesting statutorily protected leave, or any other basis protected by law. Work Authorization Requirement Applicants must have ongoing work authorization in the United States that does not require employer sponsorship. Sponsorship will not be provided now or at any time in the future for this position. Employment Eligibility Verification Legal authorization to work in the United States is required. In compliance with federal law, all persons hired must verify their identity and work eligibility and complete the required employment verification form upon hire. #J-18808-Ljbffr Profluent