Principal Scientist mRNA Design & Optimization (Billerica MA)

The businesses of Merck KGaA, Darmstadt, Germany•Billerica, MA

5h•$131,300 - $216,600•Onsite

About The Position

The Principal Scientist will join the Oligonucleotide Therapeutics team to lead the design, engineering, and optimization of therapeutic mRNAs for protein replacement, immunomodulation, vaccines, and gene-editing applications. The role leads end-to-end mRNA construct design and optimization, including UTRs, coding sequences, poly(A) tails, and cap structures, with the goal of maximizing protein expression, stability, and translational efficiency. It also develops approaches for tissue- and cell-type-specific expression and establishes workflows for mRNA synthesis, purification, characterization, and assessment of critical quality attributes. The scientist will advance mRNA cargo for the company’s LNP platform, examining how sequence and molecular properties affect encapsulation, biodistribution, and translation, particularly for immuno-oncology and immunology applications such as CAR and other engineered protein payloads. The role presents data in cross-functional meetings, collaborates across internal teams, and manages CRO/CDMO partnerships for mRNA cargo sourcing and IVT scale-up. This position will shape mRNA design capabilities and internal pipeline projects, establish design rules and screening platforms, and serve as a subject matter expert who independently defines scientific strategy. It is an on-site role in Billerica, Massachusetts.

Requirements

PhD in RNA Biology, Molecular Biology, Biochemistry, Bioengineering, Chemical Biology, Genetics, Biotechnology, or a related discipline.
Typically 5+ years of relevant industry or academic experience in RNA/mRNA therapeutics, RNA engineering, or a closely related field.
In-depth, hands-on expertise in mRNA design and sequence optimization, including UTR libraries and screening, codon optimization, miRNA/RNA-binding protein site engineering, folding, and translation enhancement.
Strong understanding of mRNA architecture and the determinants of RNA stability and translation.
Demonstrated ability to independently lead multidisciplinary projects, define scientific strategy, and solve complex technical problems.
Strong scientific communication, technical writing, and presentation skills.
Awareness of nucleic acid drug development, mRNA design, and delivery trends in the industry.
Ability to translate therapeutic-area needs into mRNA design strategies and advance internal innovation projects.
Ability to prioritize across parallel platform and pipeline projects.

Nice To Haves

Experience with tissue- and cell-specific expression optimization and modified nucleoside/base modification strategies.
Hands-on experience with in vitro transcription, mRNA synthesis, purification (e.g., chromatography and dsRNA removal), RNA characterization (CE, HPLC, LC-MS, capping and poly(A) analysis), and cellular protein-expression assays.
CAR design expertise and protein-engineering knowledge, including construct design, expression, and functional characterization.
Experience with LNP or other nucleic acid delivery systems and therapeutic areas such as immuno-oncology, immunology, or neuroscience.
Highly organized, detail-oriented, creative, results-driven problem solver with demonstrated flexibility and collaborative working style.
Familiarity with computational/in silico sequence design, folding prediction, and sequence-activity data analysis.
5+ years of pharmaceutical or biotech industry experience is strongly preferred.

Responsibilities

Lead the design, engineering, and optimization of therapeutic mRNAs for protein replacement, immunomodulation, vaccines, and gene-editing applications.
Design and optimize mRNA constructs, including 5’ UTRs, coding sequences, 3’ UTRs, poly(A) tails, and cap structures.
Generate and screen UTR libraries; optimize codons; engineer miRNA and RNA-binding-protein sites; optimize GC content, motifs, secondary structure, and folding; and control innate immune activation.
Engineer tissue- and cell-type-specific expression through regulatory element design, base and nucleoside modification strategies, and cap and poly(A) optimization.
Establish and run in vitro transcription workflows for mRNA synthesis, purification, and characterization.
Design experiments assessing mRNA integrity, purity, stability, translation, biological activity, and critical quality attributes, including capping efficiency, dsRNA, and residual impurities.
Lead projects advancing mRNA cargo for the LNP platform and evaluate how sequence, length, charge, structure, and chemical modifications affect encapsulation, biodistribution, and translation.
Present data and study updates in cross-functional project meetings.
Build the mRNA design and optimization capability, including design rules, screening platforms, and data-driven sequence optimization for LNP discovery and maturation workflows.
Independently define scientific strategy as the subject matter expert for mRNA design, optimization, and manufacture of research-grade material.
Collaborate with LNP and RNA delivery, biology, formulation, analytical, DDTech, Healthcare Research Units, and other internal teams.
Manage CRO/CDMO partnerships for mRNA cargo sourcing and IVT scale-up.
Advance internal pipeline projects on time and at high quality, including CAR and protein-engineering programs.