Senior Principal Scientist – Vector Development

Weill Cornell Medical College•New York, NY

2d•$101,000 - $126,400•Onsite

About The Position

We are seeking a motivated Senior Principal Scientist with deep expertise in viral and non-viral vector and genetic construct design to drive next-generation gene delivery strategies in a fast-paced, collaborative, and delivery-focused clinical translation research environment. This role will lead the design of lentiviral vectors, transposon-based architectures, and mRNA-based delivery systems, for applications spanning functional genomics, cell engineering, and therapeutic development. The ideal candidate combines rigorous academic training with a practical engineering mindset, capable of translating biological objectives into high-performance genetic constructs.

Requirements

PhD in Molecular Biology, Virology, Genetic Engineering, Synthetic Biology, or related field.
10+ years of relevant postdoctoral and/or industry experience in gene delivery systems or advanced molecular cloning.
Proven track record of designing and implementing complex genetic constructs.
Deep knowledge of lentiviral vector biology and design, including multi-plasmid systems and safety features.
Expertise in plasmid architecture, including promoters (e.g., EF1α, CMV, CAG), enhancers, insulators, and post-transcriptional regulatory elements.
Experience designing mRNA constructs for transient expression and delivery optimization.
Strong understanding of transposon systems and stable integration strategies.
Proficiency with DNA design software and sequence analysis tools (e.g., SnapGene, Benchling, Geneious).
Familiarity with gene expression tuning, including codon optimization, RNA stability, and translational efficiency.
Ability to interpret NGS and Sanger sequencing data for construct validation.
Engineering-driven approach to biological problem solving
High attention to detail in sequence-level design
Ability to balance innovation with practical constraints
Strong communication skills across scientific disciplines
Self-directed with a bias toward execution in a fast-moving environment

Nice To Haves

Experience with CRISPR/Cas systems, including multiplexed guide RNA architectures and delivery strategies.
Background in cell therapy, gene therapy, or genome engineering applications.
Familiarity with non-viral delivery systems (e.g., LNPs for mRNA).
Exposure to scale-up considerations and translational/regulatory frameworks.
Experience working in highly collaborative, interdisciplinary environments.

Responsibilities

Lead innovation in the design, construction, and optimization of complex plasmid systems for lentiviral vectors, including transfer, packaging, and envelope components and multi-gene cargos.
Lead engineering of novel self-inactivating (SIN) lentiviral backbones, resolving cross-element tradeoffs among LTRs, ψ (psi) packaging signal, RRE, cPPT/CTS, and WPRE.
Lead the design and implementation of innovative complex transposon-based systems, including donor vector architecture (ITRs/TIRs), multi-cargo optimization, nuclear localization and genomic integration and transposase delivery strategies.
Develop novel site-specific CRISPR/transposon integration designs.
Architect complex expression systems and establish design strategies for constitutive, inducible, cell-type-specific, and multiplexed gene expression for ex vivo and in vivo T cell engineering including CRISPR/Cas9 based delivery of mulit-gene payloads
Define and resolve platform constraints—including payload size, recombination risk, silencing, and integration profiles—and recommend fit-for-purpose delivery approaches.
Lead development and optimization of innovative mRNA delivery constructs, integrating UTRs, codon usage, modified nucleotides, cap structures, and poly(A) tail configurations to maximize stability and translation.
Provide cross-functional technical leadership across vector production, cell engineering, and functional validation teams to drive construct-design decisions and iteration.
Mentor and provide technical guidance to Scientists, Research Associates, and other laboratory personnel.
Integrate sequencing, expression, and functional data to diagnose complex packaging, delivery, or expression failures and direct corrective strategies.
Establish and oversee standards for design documentation, sequence maps, construct libraries, and design traceability.
Shape strategic direction by assessing emerging delivery modalities and synthetic biology approaches and recommending platform adoption or investment.