Senior Principal Scientist – Vector Development
Weill Cornell MedicineAbout the role
Title: Senior Principal Scientist – Vector Development
Location: Upper East Side
Org Unit: MCC Laboratories
Work Days:
Weekly Hours: 35.00
Exemption Status: Exempt
Salary Range: $101,000.00 - $126,400.00
*As required under NYC Human Rights Law Int 1208-2018 - Salary range for this role when Hired for NYC Offices
Position Summary
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.
Job 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.
Education
- PhD in Molecular Biology, Virology, Genetic Engineering, Synthetic Biology, or related field.
Experience
- 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.
Required Technical Expertise
- 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.
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
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