Upstream Principal Scientist, Vector Biology

Legend Biotech is seeking an UpstreamPrincipal Scientist, Vector Biology as part of the Vector Biology Upstream team based in Philadelphia, PA.

Role Overview

Legend Biotech seeks a highly experienced and scientifically driven Principal Scientist to join the Vector Biology Upstream team in Philadelphia, with a strategic focus on early process development and the establishment of a manufacturable lentiviral vector (LVV) platform in support of in-vivo CAR-T programs. This senior individual contributor role will serve as a scientific cornerstone within R&D, leading the early-stage definition, interrogation, and optimization of upstream LVV processes from molecular construct design through scalable bioreactor manufacturing with the deliberate intent of building a robust, developable process foundation that can be advanced into late-stage development and commercialization. The Principal Scientist will bring a rare combination of molecular biology depth and bioprocess engineering breadth, functioning as a key technical authority who bridges construct-level design decisions with upstream process outcomes, while closely interfacing with Downstream, Analytical, and Technical Development partners to ensure end-to-end process coherence and readiness for technology transfer.

Key Responsibilities

• Establish and optimize early-stage seed train strategies from shake flask through bench-scale bioreactor, defining the foundational process parameters, cell culture conditions, and operational ranges that will underpin a scalable and manufacturable LVV platform.
• Apply molecular biology expertise to evaluate LVV constructs encompassing plasmid architecture, packaging system selection, promoter and transgene configuration, and transfer vector optimization to establish high-performing, platform-compatible vectors that meet manufacturability and potency requirements for in-vivo CAR-T applications.
• Design and optimize LVV production workflows, including transient transfection systems and emerging stable producer cell line platforms, to systematically improve vector yield, product quality attributes, and process robustness as part of an integrated early process development strategy.
• Conduct systematic media optimization, feeding strategy evaluation, and bioreactor process control development to define process setpoints, identify critical process parameters (CPPs), and establish the mechanistic understanding needed to support scale-up to 40-L and beyond.
• Partner closely with Downstream colleagues to understand purification process constraints and integrate upstream design decisions including harvest conditions, clarification approaches, and vector quality attributes that enable a cohesive, end-to-end manufacturable process. 
• Design and execute fit-for-purpose early process development studies to generate the foundational data packages required for process lock, comparability assessments, and downstream regulatory filings; apply structured Design of Experiments (DoE) and risk-based approaches to maximize information yield.
• Serve as the upstream scientific lead within Vector Biology, providing authoritative technical input to cross-functional forums on construct-process relationships, early development strategy, and the stage-appropriate advancement of research findings into formal process development programs aligned with IND-enabling timelines.
• Exercise a high degree of scientific independence in designing and executing complex experiments; proactively identify technical risks, generate mechanistic hypotheses, and implement data-driven solutions with minimal oversight to keep early development programs on track.
• Synthesize complex experimental datasets into clear, structured data packages and deliver evidence-based technical recommendations that drive go/no-go decisions, inform process development strategy, and support program progression within Vector Biology and across R&D functional teams.
• Author high-caliber technical reports, early process development summaries, and stage-gate presentations that communicate scientific progress, key process decisions, and development risk assessments to Vector Biology leadership and cross-functional R&D stakeholders.
• Operate in full adherence to BSL-2 biosafety requirements and Legend Biotech’s research policies; maintain rigorous, contemporaneous electronic laboratory notebook records that meet scientific reproducibility standards and support future transition into GxP-aligned development stages.
• Champion experimental reproducibility and data integrity through rigorous, organized documentation practices that meet the highest standards of scientific rigor and regulatory traceability.
• Apply molecular biology expertise to design, engineer, and evaluate LVV constructs encompassing plasmid architecture, packaging system selection, promoter and transgene configuration, and transfer vector optimization to establish high-performing, platform-compatible vectors that meet manufacturability and potency requirements for in-vivo CAR-T applications.

Requirements

• MS degree with 10+ years; or PhD degree with ~5-8+ years of progressive industry experience in Bioengineering, Cell Biology and Chemical Engineering, or a closely related discipline. Advanced degree (PhD) with a molecular biology or virology foundation is preferred for this Principal Scientist role in early process development.
• Demonstrated hands-on expertise in viral vector production, upstream process development, and characterization across multiple development scales, with a clear track record of translating early research-stage processes toward manufacturable, scalable platforms (required).
• Substantial experience in mammalian suspension cell culture and upstream bioprocessing, with meaningful exposure to molecular biology workflows relevant to viral vector construct engineering.
• Experience with bioreactor operations (up to 50 L preferred) and familiarity with downstream processing operations including clarification, chromatographic purification, and tangential flow filtration with the ability to apply downstream process constraints to upstream design decisions is a strong differentiator. 
• Meaningful early process development experience within gene therapy or viral vector platforms, with direct hands-on contribution to defining manufacturable upstream processes from concept through bioreactor scale.
• Exceptional analytical acumen and structured scientific reasoning; experienced in the application of Design of Experiments (DoE), multivariate data analysis, and risk-based decision frameworks to accelerate early process development and maximize learning efficiency.
• Demonstrated commitment to scientific rigor and research data integrity, with proficiency in maintaining meticulous, contemporaneous electronic laboratory notebook records that ensure experimental reproducibility and are structured to support future GxP-aligned technology transfer activities.
• Highly organized and execution-oriented, with demonstrated capacity to manage multiple concurrent early development workstreams, prioritize effectively in a fast-paced R&D environment, and deliver scientifically sound results within program-driven timelines.
• Exemplary oral and written communication skills, with the ability to translate complex early process development findings into compelling scientific narratives for diverse audiences including R&D leadership, CMC colleagues, and cross-functional program teams while operating with equal effectiveness as a self-directed scientific contributor and an engaged collaborative partner
• Proficiency in molecular biology techniques central to viral vector construct design, including plasmid architecture and engineering, packaging system configuration, promoter selection and regulatory element optimization, transgene design, and transfer vector development to support LVV platform optimization (preferred).
• Working knowledge of downstream processing operations —encompassing harvest and clarification strategies, affinity and ion-exchange chromatography, and tangential flow filtration — with the scientific acuity to incorporate purification process requirements and vector quality attribute targets into upstream process design; experience in integrated upstream-downstream process development is preferred.

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