Principal Scientist, Advanced In Vitro Platforms

OverviewWe are seeking an accomplished and motivated Principal Scientist to lead innovation in advanced in vitro modeling to enable RNAi discovery and development. In this role, you will be responsible for designing, validating, and implementing physiologically relevant model systems-such as iPSC-derived models, organoids, and microphysiological systems (MPS)-to enhance biological predictivity, deepen mechanistic understanding, and increase translational confidence across multiple therapeutic areas.The ideal candidate will have a strong background in cellular and molecular biology, experience with complex in vitro model development, and a passion for leveraging advanced systems to drive impactful RNAi therapeutics.This position isonsiteand will be primarily located in Cambridge, MA.Key ResponsibilitiesLead and mentor the Advanced In Vitro Delivery group, fostering scientific excellence and ensuring the team remains at the forefront of emerging technologies and methodologies. Shape scientific strategy by staying current with advances in RNAi therapeutics and contributing to the strategic direction of discovery and platform development efforts. Collaborate cross-functionally with internal teams and CRO partners to develop, validate, and implement advanced in vitro systems-including 2D, 3D, organoid, and organ-on-a-chip models-that are predictive of in vivo siRNA uptake and biological activity. Drive experimental execution, including design, implementation, and troubleshooting of complex in vitro studies to evaluate siRNA delivery and mechanism of action. Provide technical leadership in the development and deployment of next-generation in vitro modeling technologies across multiple tissue types. Adapt and miniaturize advanced cell culture systems for automated, high-throughput screening applications. Perform and oversee analytical assays, including imaging, ELISA, Western blotting, and cell-based functional assays, to assess siRNA delivery efficiency and receptor-mediated uptake. Analyze and interpret data, integrating imaging and functional readouts, and effectively communicate results to internal stakeholders and external collaborators. Partner with discovery teams to integrate validated in vitro models into RNAi screening and lead optimization workflows.QualificationsPh.D. in Cell Biology, Pharmacology, or a related discipline with 6+ years of hands-on industry experience in a biotechnology or pharmaceutical environment. Demonstrated expertise in ex vivo cell assays, microphysiological systems (MPS), primary and iPSC-derived cell culture, and cell-based functional assays. Strong understanding of in vitro assay development and the application of 2D and 3D culture systems to model and predict in vivo siRNA delivery, uptake, and activity. Proven experience with 3D culture platforms, including spheroids, organoids, and co-culture models. Exceptional organizational and analytical skills, with the ability to independently troubleshoot, optimize, and innovate experimental approaches. Effective team collaborator and communicator, capable of presenting scientific findings clearly to diverse audiences. Self-driven and proactive, with the ability to lead projects, manage multiple priorities, and adapt to evolving objectives in a fast-paced environment. Strong project management and leadership skills, with a proven ability to lead teams and deliver results through cross-functional collaboration. Experience with oligonucleotide or RNAi-based therapeutics is highly desirable.#LI-JR1 U.S. Pay Range $147,200.00 - $220,800.00 The pay range reflects the full-time base salary range we expect to pay for this role at the time of posting. Base pay will be determined based on a number of factors including, but not limited to, relevant experience, skills, and education. This role is eligible for an annual short-term incentive award (e.g., bonus or sales incentive) and an annual long-term incentive award (e.g., equity). Alnylam's robust Total Rewards package is designed to support your overall health and well-being. We offer comprehensive benefits including medical, dental, and vision coverage, life and disability insurance, a lifestyle reimbursement program, flexible spending and health savings accounts and a 401(k)with a generous company match. Eligible employees enjoy paid time off, wellness days, holidays, and two company-wide recharge breaks. We also offer generous family resources and leave. Our commitment to your well-being reflects our belief that caring for our people fuels the impact we create together. Learn more about these and additional benefits offered by Alnylam by visiting theBenefits section of Nebula . >