Senior Scientist / Principal Scientist, mRNA Molecule Design and Platform Innovation

Company Description

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We are a privately held, stealth-mode start-up biotechnology company developing lipid nanoparticle–based approaches to address unmet medical needs across oncology, hematology, and neuroscience.

The Role

We are seeking an exceptionally driven, discovery-minded Senior Scientist / Principal Scientist to lead mRNA molecule design and platform innovation. This role sits at the front end of our innovation engine: inventing, engineering, and systematically optimizing the mRNA molecules that define what our platform can deliver, and moving those advances rapidly into pipeline programs.

The successful candidate will own the design and engineering of mRNA payloads, from untranslated regions, open reading frames, and codon usage through cap structures, poly(A) tail configurations, and RNA secondary structure, with the goal of maximizing expression, stability, translational efficiency, and in vivo performance. Beyond sequence-level optimization, this person will explore next-generation mRNA architectures and design the screening strategies that drive rapid, rigorous design iteration.

This is a hands-on experimental role with a strong computational and cross-functional dimension. The ideal candidate brings deep expertise in RNA biology and mRNA engineering, a rigorous and creative scientific mindset, and a genuine commitment to translating breakthrough science into medicines. This person will partner closely with LNP formulation, analytical, process development, and program teams to carry designs from concept through development candidate nomination. As the portfolio grows, the scope of this role is expected to grow with it.

This position is open at the Senior Scientist or Principal Scientist level. The scientific scope and responsibilities are the same at both levels; the distinction is based on depth of experience and demonstrated independence, technical leadership, and influence across programs.

Roles and Responsibilities

mRNA Sequence Engineering and Molecule Design

• Design, construct, and systematically optimize mRNA molecules, including 5' and 3' UTR sequences, open reading frame and codon usage optimization, cap structures, poly(A) tail configurations, nucleoside modifications, and RNA secondary structure, individually and in combination, to maximize protein expression, stability, and translational efficiency.
• Own the translation of payload concepts into manufacturable, well-characterized constructs; Closely work with DS PD team to execute molecular cloning, in vitro transcription (IVT), purification, and RNA characterization at research scale.
• Establish and apply design rules that connect mRNA sequence and structural features to expression, durability, and tolerability outcomes across cell types and tissues.

Platform Innovation and Screening Design

• Design screening strategies that compare design variants efficiently and rigorously, enabling rapid iteration from design hypothesis to interpretable data.
• Identify, evaluate, and implement new reagents, chemistries, and technologies that improve payload performance, manufacturability, and speed from design to data.
• Maintain active engagement with the scientific literature and emerging technologies in mRNA engineering, RNA biology, and nucleic acid therapeutics to anticipate the next wave of innovation and identify external advances or collaborations worth pursuing.

Structure-Function Analysis and Computational Design

• Design and execute well-controlled experiments to probe structure-function relationships in mRNA payloads; generate clean, interpretable data that drives platform design decisions.
• Apply or partner on computational and AI/ML approaches to RNA secondary structure prediction, sequence optimization, and prediction of drug-like properties; help build the internal datasets that make these models useful.
• Establish quantitative assays and analysis frameworks that make design comparisons rigorous and reproducible across campaigns.

Cross-Functional Partnership

• Partner with discovery team to drive candidate mRNA designs from in vitro screening into in vivo evaluation, and iterate designs based on pharmacology and biodistribution data.
• Partner with the LNP formulation team to co-optimize payload and delivery system, recognizing that molecule design and delivery performance cannot be optimized in isolation.
• Partner with analytical development and process development to ensure designs are characterizable and manufacturable, providing design input on payload size, modification chemistry, secondary structure, and DNA template considerations.
• Collaborate with CMC teams, external collaborators, and CROs to translate platform advances into program-specific solutions, including supporting development candidate nominations.
• Communicate research findings clearly to internal scientific audiences; contribute to publications, patent filings, and conference presentations that advance the company's scientific profile.
• Mentor and provide day-to-day scientific direction to research associates and junior scientists, with potential oversight of additional staff as the team scales; contribute to a culture of scientific excellence, intellectual curiosity, and collaborative problem-solving.
• Adhere to all laboratory safety requirements and procedures; author, review, and maintain accurate laboratory notebooks.

Required Qualifications

• PhD in molecular biology, biochemistry, RNA biology, chemical biology, bioengineering, or a related discipline, with 5+ years (Senior Scientist) or 7+ years (Principal Scientist) of relevant postdoctoral and/or drug discovery industry experience.
• Deep hands-on expertise in mRNA biology and engineering, including practical experience with in vitro transcription (IVT), UTR design and optimization, codon usage, capping and poly(A) strategies, RNA secondary structure, and the relationship between mRNA sequence design and protein expression outcomes.
• Strong hands-on molecular biology skills, including molecular cloning, DNA template design and generation, and RNA characterization and performance assays.
• Demonstrated track record of designing and executing well-controlled structure-function studies and drawing clear, actionable conclusions from them.
• Experience translating RNA-based therapeutics from in vitro systems into in vivo animal models using non-viral delivery, preferably LNP.
• Experience working in a collaborative, cross-functional research environment, with the ability to contribute meaningfully to team science while driving individual workstreams autonomously.
• Excellent scientific communication skills, with the ability to present complex findings clearly to diverse audiences; strong publication and presentation record.
• Ability to leverage literature, internal and external resources to solve problems and develop new technologies.

Preferred Qualifications

• Experience applying computational tools or AI/ML approaches to mRNA sequence design, structure prediction, or property optimization is a strong plus; familiarity with relevant bioinformatics tooling and scripting is highly valued.
• Understanding of how payload design choices propagate into process development, analytical characterization, and CMC requirements.
• Experience designing and running screening campaigns for nucleic acid design.
• Experience with next-generation or engineered RNA formats, including circular RNA, self-amplifying RNA, or related modalities.
• Familiarity with gene editing payloads and precision genetic medicine approaches, including CRISPR-based, base editing, or prime editing systems.
• Working knowledge of human biology and animal models of disease as they relate to therapeutic development.
• Experience providing day-to-day scientific direction to research associates, interns, or co-op students, and comfort collaborating with and directing the work of external CROs.
• A bias toward proactive problem-solving and a collaborative mindset suited to a small, high-velocity team. xhyhwjd

Location

San Diego, CA. This is an on-site position.

What We Offer

• An opportunity to work at the forefront of RNA and LNP-based therapeutic innovation
• A collaborative, science-first culture where individual contributions are visible and impactful
• Competitive compensation and benefits package, including health, dental, vision, and life insurance
• 401(k) with company match