Upstream Principal Scientist, Vector Biology

Legend Biotech is a global biotechnology company dedicated to treating, and one day curing, life-threatening diseases. Headquartered in Somerset, New Jersey, we are developing advanced cell therapies across a diverse array of technology platforms, including autologous and allogenic chimeric antigen receptor T-cell, T-cell receptor (TCR-T), and natural killer (NK) cell-based immunotherapy. From our three R&D sites around the world, we apply these innovative technologies to pursue the discovery of safe, efficacious and cutting-edge therapeutics for patients worldwide. Legend Biotech entered into a global collaboration agreement with Janssen, one of the pharmaceutical companies of Johnson & Johnson, to jointly develop and commercialize ciltacabtagene autolecuel (cilta-cel). Our strategic partnership is designed to combine the strengths and expertise of both companies to advance the promise of an immunotherapy in the treatment of multiple myeloma. Legend Biotech is seeking an Upstream Principal 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 a