Principal Scientist mRNA Design & Optimization (Billerica MA)

Merck•Billerica, MA

8d•Onsite

About The Position

The Principal Scientist will join EMD Serono’s Oligonucleotide Therapeutics team to lead the design, engineering, and optimization of therapeutic mRNAs for protein replacement, immunomodulation, vaccines, and gene-editing applications. The role involves designing mRNA constructs end-to-end, including the 5′ UTR, coding sequence, 3′ UTR, poly(A) tail, and cap structure, to maximize protein expression, stability, and translational efficiency. Work includes UTR library generation and high-throughput screening, codon optimization, miRNA and RNA-binding-protein site engineering, GC content and motif design, secondary-structure optimization, and control of innate immune activation. The scientist will engineer tissue- and cell-type-specific expression through regulatory element design, base and nucleoside modification strategies, and cap/poly(A) optimization. The role also establishes and runs in vitro transcription (IVT), mRNA synthesis, purification, and characterization workflows, and designs experiments to assess integrity, purity, stability, translation, biological activity, and critical quality attributes. The scientist will lead projects advancing mRNA cargo for the company’s LNP platform, evaluating how sequence, length, charge, structure, and chemical modifications affect encapsulation, biodistribution, and translation, with a focus on immuno-oncology and immunology applications, including CAR and other engineered protein payloads. The position shapes mRNA design and optimization capabilities, including design rules, screening platforms, and data-driven sequence optimization, and independently defines scientific strategy as a subject matter expert. It also involves presenting data and study updates, collaborating across internal teams and research units, and managing CRO/CDMO partnerships for mRNA cargo sourcing and IVT scale-up. The role is on-site 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 determinants of RNA stability and translation.
Demonstrated ability to lead multidisciplinary projects independently, 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.
Familiarity with computational/in silico sequence design, folding prediction, and sequence-activity data analysis.
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 IVT, mRNA synthesis, purification (such as chromatography and dsRNA removal), RNA characterization (including 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.
5+ years of pharmaceutical or biotech industry experience is strongly preferred.

Responsibilities

Lead design, engineering, and optimization of therapeutic mRNAs for protein replacement, immunomodulation, vaccines, and gene-editing applications.
Design and optimize mRNA constructs, including UTRs, coding sequence, poly(A) tail, and cap structure, using library screening, codon optimization, site engineering, motif and GC-content design, folding optimization, and innate immune activation control.
Engineer tissue- and cell-type-specific expression using regulatory elements, base and nucleoside modifications, and cap/poly(A) optimization.
Establish and run IVT, mRNA synthesis, purification, and characterization workflows.
Design experiments assessing mRNA integrity, purity, stability, translation, biological activity, and critical quality attributes.
Lead projects advancing mRNA cargo for the LNP platform and evaluate how cargo properties affect encapsulation, biodistribution, and translation.
Present data and study updates in cross-functional project meetings.
Build and own the mRNA design and optimization capability, including design rules, screening platforms, and data-driven sequence optimization.
Independently define scientific strategy for mRNA design, optimization, and manufacture of research-grade material.
Collaborate with LNP and RNA delivery, biology, formulation, analytical, DDTech, Healthcare Research Unit, CAR, and protein engineering teams on projects.
Manage CRO/CDMO partnerships for mRNA cargo sourcing and IVT scale-up.
Prioritize and advance parallel platform and pipeline projects.