Scientist I/II, Modality Engineering

Role Summary

Lexeo is hiring a hands-on Modality Engineering Scientist to design, synthesize, and characterize oligonucleotides, bioconjugates, and AAV therapeutics for our discovery pipeline. The scientist will advance molecules from design through analytical characterization and handoff to in vitro and in vivo teams, working across chemistry, molecular biology, and pharmacology. Reporting to the Head of Cardiac Research, this role joins cardiac, neuroscience, and non-clinical scientists developing therapies for genetic heart disease and offers broad experience in multidisciplinary biopharma research.

Primary Responsibilities

• Select and manage CROs for oligonucleotide synthesis and bioconjugation, including scope, vendor guidance, data review, quality, and delivery timelines
• Design and oversee oligonucleotide conjugates using peptides, antibodies, or ligands; optimize conjugation chemistry, linkers, purification, and analytical characterization
• Build or outsource methods to confirm identity and assess purity using HPLC, LC-MS, SDS-PAGE, spectroscopy, and other fit-for-purpose assays
• Engineer AAV capsids, regulatory elements, and transgene cassettes; conduct cloning, plasmid preparation, sequencing, and research-grade vector production
• Design and screen sequence or vector/capsid with NGS readouts, applying state-of-the-art analytical methods to improve potency, selectivity, and production yield
• Partner with In Vitro Pharmacology, In Vivo Physiology, Analytical DMPK, and CMC to define screening cascades, interpret data, assess developability and manufacturability, select leads, and support go/no-go decisions
• Support molecule advancement through process development and formulation while identifying technical risks and recommending practical experiments or external capabilities
• Write SOPs, maintain and troubleshoot instruments, document work in the ELN for intellectual property and regulatory filings, present results, and monitor platform advances

Required Skills and Qualifications

• PhD in chemistry, chemical biology, biochemistry, molecular biology, or a related field with 0-3 years of postdoctoral or industry experience; or MS with 5+ years of industry experience
• Hands-on experience synthesizing, purifying, and characterizing research-scale ASOs, siRNAs, or bioconjugates using automated solid-phase synthesis, chromatography, and mass spectrometry
• Working knowledge of ASO/siRNA therapeutic chemistry, backbone and sugar modifications, class-related toxicity, various delivery approaches
• Strong research productivity demonstrated through publications, patent filings, or comparable technical contributions
• Clear written and verbal communication skills, sound scientific judgment, and the ability to manage multiple projects in a collaborative, fast-paced team
• Ability to regularly work onsite at our HQ in New York City

Preferred Skills and Qualifications

• Industry experience in a small, fast-paced biotech is highly preferred
• Working knowledge of AAV biology and vector design
• Hands-on experience in AAV capsid engineering, pooled library design, and NGS data analysis
• Antibody- or peptide-oligonucleotide conjugate (AOC/POC) design or linker discovery