Senior Scientist Nucleoside Chemistry

Your Role

The Oligonucleotide Therapeutics group of EMD Serono in Billerica, MA, is seeking a highly motivated and collaborative Senior Scientist to lead the design and synthesis of nucleoside-based molecules and conjugates that improve intracellular delivery, with a particular focus on endosomal escape agents. The successful candidate will utilize their strong synthetic chemistry expertise, sound judgment in molecular design, and their ability to work closely with Oligonucleotide synthesis, analytical, and formulation colleagues to advance promising concepts from early discovery through lead optimization. This role is intended for an experimental nucleoside and medicinal chemist who combines a strong foundation in and hands-on experience in the synthesis of novel nucleoside analogs, peptide and small molecules. In this role, you will help advance novel oligonucleotide therapeutics from early discovery toward preclinical development by developing robust in vitro assays, generating high-quality biological data, and contributing to the selection of next-generation therapeutic candidates.

Responsibilities

• Design and synthesize nucleoside analogues, functionalized building blocks, linkers, and conjugates for intracellular delivery applications.
• Design and synthesize 2’F nucleoside analogs and related modified nucleoside building blocks for incorporation into oligonucleotides.
• Develop and optimize chemistry for 5′-phosphate-modified oligonucleotides, including suitable building blocks, reagents, and on-support or post-synthetic modification workflows as appropriate to the project.
• Develop and evaluate molecular strategies for endosomal escape, including approaches to tune charge, hydrophobicity, ionization, degradability, and target-payload association.
• Plan and execute multistep synthesis, purification, and structural characterization; troubleshoot challenging reactions and improve routes for reproducibility, yield, and material quality.
• Apply appropriate analytical methods to confirm identity, purity, stability, and conjugate composition; maintain clear and complete experimental records.
• Drive innovation to improve circulating half-life, tissue penetration, cellular uptake, and intracellular bioavailability of payloads.
• Present project updates, technical recommendations, and risks to multidisciplinary teams; author reports and contributes to invention disclosures and publications as appropriate.
• Collaborate with cross-functional teams including computational chemistry, biology, and pharmacology to drive project success.

Minimum Qualifications

PhD in Medicinal Chemistry, Synthetic Organic Chemistry, Chemical Biology, or other Science field with 5+ years of experience in nucleoside chemistry.

Preferred Qualifications

• Demonstrated expertise in multistep organic synthesis and a record of delivering complex molecules or conjugates.
• Practical experience with nucleoside chemistry and/or bioconjugation, linker design, or payload conjugation.
• Strong understanding of how molecular properties can affect solubility, stability, membrane interaction, cellular uptake, and intracellular trafficking.
• Familiarity with 5′-end functionalization or phosphorylation chemistry, or the ability to develop and optimize such methods.
• Proficiency with routine compound characterization and analytical techniques, such as NMR, LC–MS, HPLC, and related methods.
• Excellent scientific communication, project planning, and problem-solving skills; ability to work independently while contributing to shared goal.
• Exceptional communication skills with the ability to translate complex data into internally as well as with CRO’s.