Head of Oligonucleotides

Description

Gensaic combines AI-powered protein design with unbiased directed evolution to develop tissue-selective ligands for targeted intracellular therapeutic delivery. The company's portfolio advances therapies for metabolic and age-related diseases, with an initial focus on siRNA payloads. FORGE™, Gensaic's proprietary product engine, integrates phage libraries for unbiased protein evolution within a generative AI architecture to discover and optimize protein and peptide molecules with enhanced tissue selectivity and drug-like properties. Founded at MIT and based in Cambridge, Massachusetts, Gensaic's team of physicians, bioengineers, and machine learning scientists is advancing a singular objective: to enable selective delivery of any therapeutic payload to any tissue of interest. We are an early-stage startup and look for people who are passionate about science, community and doing good.

For more information, please visit gensaic.com.

Location

Cambridge, MA

Summary

We are seeking an accomplished Head of Oligonucleotides with a strong background in nucleic acid chemistry and therapeutic design to join our research and development team. The ideal candidate will bring both chemical and biological insight to the design, synthesis, and optimization of therapeutic oligonucleotides—including siRNA, antisense (ASO), and PMO modalities. This role requires deep understanding of computational sequence design, chemical modification strategies, screening workflows, and peptide/protein conjugation methodologies that drive lead identification and optimization for RNA-targeted drug programs. The candidate will lead efforts to translate gene target hypotheses into optimized, manufacturable drug candidates, contributing to the expansion of the oligonucleotide therapeutic pipeline.

Key Responsibilities

Target Selection

• Apply critical scientific reasoning to select, validate, and prioritize genetic targets for oligonucleotide intervention.
• Design multi-parameter screening workflows for potency, selectivity, and manufacturability across siRNA, ASO, and PMO platforms.
• Integrate sequence informatics, chemical modification patterns, and structure–function insights to rationalize design hypotheses.
• Partner with computational and translational teams to connect in vitro efficacy with in vivo and clinical relevance.

Sequence Design & Optimization

• Use bioinformatics and predictive modeling tools to design oligonucleotides with optimal target engagement and minimal off-target activity.
• Iterate designs based on chemical modification, thermodynamic, and pharmacokinetic principles to improve stability, safety, and tissue distribution.
• Innovate in backbone, sugar, and conjugation chemistries to enhance delivery and cellular uptake.

Assay Development & Screening

• Collaborate with internal or external chemistry teams on oligonucleotide synthesis, purification, and analytical characterization.
• Lead high-throughput screening campaigns in cellular and animal models to assess efficacy, stability, and specificity.
• Lead or support validation assays for target engagement, mRNA knockdown, and downstream functional effects.
• Develop and implement functional assays to test target biology and clinical hypotheses.

Cross-functional Integration

• Contribute to early-stage buildout of the oligonucleotide therapeutic pipeline, from concept to lead nomination.
• Collaborate with teams in delivery, chemistry, bioinformatics, and pharmacology to define screening funnels and development decision criteria.
• Critically evaluate data to identify promising leads and propose next-generation design iterations.
• Author internal reports, presentations, patent filings, and contribute to IND-enabling documentation.

Qualifications & Experience

Education: Ph.D. in Chemistry, Biochemistry, Medicinal Chemistry, or related field.

Experience:

• 6 years of industry experience in oligonucleotide drug discovery, medicinal chemistry, or nucleic acid chemistry.
• Deep understanding of nucleic acid chemical modifications, hybridization thermodynamics, and degradation pathways.
• Demonstrated track record in siRNA, ASO, or PMO sequence design and optimization.
• Proven ability to interpret biological data and link it to chemistry-driven design improvements.
• Hands-on experience in solid-phase oligonucleotide synthesis, purification, and analytical characterization.
• Familiarity with computational design, RNA secondary structure prediction, and off-target analysis tools.

Preferred Skills

• Strong conceptual understanding of gene target biology and delivery mechanisms.
• Knowledge of peptide, lipid, or antibody conjugation strategies for tissue targeting.
• Familiarity with peptide chemistry and production.
• Experience integrating bioinformatics and high-content screening data to drive design refinement.
• Familiarity with automation workflows, assay miniaturization, and data-driven screening optimization.
• Proficiency with Python, R, or sequence design software for oligonucleotide analysis.
• Previous drug development experience in biotechnology, pharmaceuticals, or synthetic biology.
• Experience in lipid nanoparticles (LNPs), polymer-based, or exosome-based oligonucleotide delivery systems.
• Working knowledge of oligonucleotide manufacturing and CMC considerations.

Personal Attributes

• Strong analytical and critical thinking skills—able to integrate complex data sets into actionable insights.
• Chemistry-first mindset combined with appreciation for biological context and translational impact.
• Strategic mindset for building and prioritizing early oligonucleotide pipelines.
• Collaborative communicator who thrives in a multidisciplinary environment.
• Innovative, rigorous, and detail-oriented, with a passion for developing transformative genetic medicines.

Why Join Us?

• Opportunity to work on cutting-edge protein and oligonucleotide engineering, therapeutic conjugation, and screening technologies.
• Collaborative and inclusive research environment with opportunities for professional growth.
• Competitive compensation, benefits, and career development support.
• Make a meaningful impact on innovative therapeutics and next-generation biologics.

If you are passionate about protein and oligonucleotide engineering and thrive in an interdisciplinary and fast-paced research setting, we encourage you to apply!

Cutlture at Gensaic

‘A place where everybody knows your name’

·      Care about people and obsess about the science

·      Celebrate diversity in everything    

·      Always communicate 

·      Show empathy and respect   

·      Deliver value

·      Admit mistakes and shortcomings

·      Sweat the details

·      Laugh

Perks and Benefits

Work with a talented and collaborative team   

Competitive compensation & equity package

401k, Medical, dental, and vision insurance

Continued education and conferences stipend

Wellness (and why not) stipend

We are an equal opportunity employer and value diversity at our company. We do not discriminate on the basis of race, religion, color, national origin, gender, sexual orientation, age, marital status, veteran status, or disability status.