Scientist - Oligonucleotide Biology

Merck•Billerica, MA

5d•Onsite

About The Position

The Oligonucleotide Therapeutics group is seeking a highly motivated and collaborative Scientist to support the discovery, characterization, and optimization of oligonucleotide therapeutics across a range of disease areas. This role is intended for an experimental molecular and cellular biologist who combines a strong foundation in RNA biology with hands-on experience in cell-based assay development, mechanistic studies, and translational research. 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. You will be responsible for designing, executing, and optimizing cellular and molecular biology workflows to evaluate oligonucleotide activity, including target engagement, mRNA knockdown, protein modulation, and mechanism of action. You will establish quantitative molecular biology workflows, optimize cell-based assay platforms, and apply data-driven insights to support candidate prioritization and translational decision-making. Working closely with chemistry, formulation, and translational research teams, you will help evaluate novel oligonucleotide sequences, chemical modifications, and delivery strategies while contributing to the advancement of our oligonucleotide therapeutic platform.

Requirements

PhD in Molecular Biology, Cell Biology, RNA Biology, Biochemistry, Pharmacology, or other Scientific discipline with 1+ years of experience with oligonucleotide therapeutics, including ASOs, siRNA, miRNA, splice-switching oligonucleotides, or similar RNA-targeting technologies OR Master’s degree in Molecular Biology, Cell Biology, RNA Biology, Biochemistry, Pharmacology, or other Scientific discipline with 3+ years of experience with oligonucleotide therapeutics, including ASOs, siRNA, miRNA, splice-switching oligonucleotides, or similar RNA-targeting technologies

Nice To Haves

Experience culturing and maintaining mammalian cell lines and developing robust cell-based assays for therapeutic discovery
Strong experience developing and executing cell-based assays to evaluate target engagement, gene expression, and pharmacodynamic endpoint
Proficiency in molecular and cellular biology techniques including RT-qPCR, Western blotting, ddPCR, ELISA/MSD immunoassays, flow cytometry, fluorescence microscopy, and mammalian cell culture
Experience designing, optimizing, and executing medium- to high-throughput cell-based screening assays using multiple mammalian cell lines to evaluate oligonucleotide potency, target engagement, and pharmacodynamic responses
Familiarity with oligonucleotide chemical modifications, delivery technologies, and mechanism-of-action studies
Experience with laboratory automation, high-throughput screening, or Design of Experiments (DoE)
Knowledge of translational biomarkers, pharmacodynamic assays, and target engagement strategies
Demonstrated ability to independently design experiments, analyze complex datasets, troubleshoot technical challenges, and communicate scientific findings
Excellent organizational, written, and verbal communication skills
Ability to work effectively in a collaborative, cross-functional research environment

Responsibilities

Design, execute, and optimize in vitro assays to evaluate oligonucleotide (ASO, siRNA, LNA) activity, including target engagement, mRNA knockdown, protein modulation, and splice-switching in disease-relevant cell models.
Establish, optimize, and validate molecular biology workflows including RT-qPCR, Western blotting, flow cytometry, immunofluorescence microscopy, and other cell-based assays to support therapeutic discovery.
Develop and characterize cellular models to assess oligonucleotide uptake, intracellular trafficking, pharmacodynamic responses, and mechanism of action.
Perform dose-response and time-course studies to evaluate oligonucleotide potency, durability, and pharmacological activity.
Analyze experimental data, identify trends, troubleshoot technical challenges, and recommend next-step experiments to advance lead optimization.
Collaborate with multidisciplinary teams, including chemistry, formulation, and bioinformatics, to evaluate oligonucleotide sequences, chemical modifications, and delivery strategies.
Support implementation of laboratory automation and high-throughput workflows to improve assay robustness, reproducibility, and efficiency.
Maintain accurate experimental records and document procedures, results, and conclusions in accordance with internal standards and good laboratory practices.
Present scientific findings at project team meetings and contribute to internal reports, scientific presentations, and publications.
Maintain a safe, organized laboratory environment while adhering to company safety policies and laboratory best practices.