Senior Principal Scientist - Vector Development

Location: Upper East Side, NYC. Exempt role, 35 hours/week. Salary range: $101,000 – $126,400.

About the role

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.

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.
• Engineer novel self-inactivating (SIN) lentiviral backbones, resolving cross-element tradeoffs among LTRs, ψ (psi) packaging signal, RRE, cPPT/CTS, and WPRE.
• Design and implement innovative complex transposon-based systems, including donor vector architecture (ITRs/TIRs), multi-cargo optimization, nuclear localization, 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 multi-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.

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.

Skills

• 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.

Preferred Qualifications

• 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.

Working Conditions

Operates at the interface of academia and biotech: hypothesis-driven research combined with milestone-oriented execution. Access to cutting-edge genomic technologies and collaborative expertise. Emphasis on rapid iteration, data-driven decision making, and translational impact.