Scientist II, mRNA Technologies

Published: 6/14/2022

Technology

Job Description

Repertoire Immune Medicines is a clinical-stage biotechnology company harnessing the power of the human immune system to develop transformative therapies for cancer and autoimmune disease. Using its proprietary DECODETM platform—which maps the immune synapse between T cell receptors (TCRs) and their antigen targets—Repertoire translates unique biological insights into potent and targeted off-the-shelf immune medicines. The company integrates deep protein engineering expertise with artificial intelligence, powered by a proprietary DECODE database of over one billion TCR-antigen interactions, to accelerate discovery and optimize drug candidates.

From its sites in Watertown, Massachusetts and Zurich, Switzerland, Repertoire is advancing a pipeline of T cell-targeted immunotherapies with the potential to address a broad range of cancers and autoimmune disorders. The company’s lead oncology program, RPTR-1-201, a TCR bispecific, has initiated a Phase 1/2 clinical trial across multiple solid tumor indications. Repertoire plans to advance additional TCR bispecific therapies into clinical trials over the next 12-18 months. In autoimmune disease, Repertoire is partnering with leading pharmaceutical companies to develop mRNA tolerizing therapies designed to selectively expand regulatory T cells and reset the immune system.

Repertoire was founded in 2019 by Flagship Pioneering and is supported by a strong investor base. The DECODE platform has been validated through four strategic partnerships with leading pharmaceutical companies—Bristol Myers Squibb, Genentech, Eli Lilly, and Pfizer—representing over $4.5 billion in disclosed total deal value and $185 million in upfront payments received to date.

Role Overview
We are seeking a highly skilled and motivated Scientist II to join Repertoire’s autoimmune tolerance induction team. Working with a dedicated team of scientists and research associates, you will help advance Repertoire’s novel immune tolerance modality across multiple indications.

You will lead the design, development, and optimization of mRNA constructs that deliver antigens, cell-modifying payloads, and immune modulators across concurrent autoimmune programs. Opportunities to drive innovation include optimizing protein expression, immune epitope presentation, and silencing of innate immune signaling.

As part of the Integrated Therapeutics and Development team (ITED), you will partner closely with lipid nanoparticle technology, in vivo pharmacology, antigen discovery and validation, and computational sciences to advance drug candidates from concept through preclinical and toward clinical development.

The ideal candidate will have experience in the design, production, purification, and molecular and functional characterization of therapeutic mRNA, including UTR and ORF design, as well as an interest in developing high-throughput in vivo assays to assess payloads and delivery vehicles. Experience with analytical assessment of mRNA drug substance and mRNA-LNP drug product is ideal. The successful candidate will be motivated by creating highly active therapeutic molecules and by establishing a production capability to support research within the tolerance team and across Repertoire.

Working with the broader team, you will drive projects and programs from discovery through preclinical and IND-enabling studies. Success in this role requires strong interpersonal, verbal, and written communication skills; experimental rigor and scientific curiosity; and the ability to work in a fast-paced, matrixed environment and adapt to evolving priorities.

Key Responsibilities

Design and optimize the molecular components of mRNA molecules for antigen expression and presentation in immune cells, as well as in other tissue targets for systemic protein delivery.
Collaborate with preclinical biology and disease area teams on characterizing construct designs and payloads for functional activity across in vitro and in vivo models.
Establish, optimize, and innovate processes for scalable in vitro transcription (IVT) production and purification of mRNA for discovery and therapeutic applications.
Contribute to the development of analytical characterization methods for mRNA molecules and mRNA-LNP drug product with an eye toward tech transfer to a CRO/CDMO.
Ensure supply of in vivo grade mRNA and mRNA-LNP product to the tolerance team and throughout Repertoire.
Design and maintain the external supply chain for research grade plasmids for IVT production of mRNA.
Cross-train with the LNP team to support LNP production and characterization (e.g., particle size and surface charge measurements, and endotoxin testing) to meet project timelines.
Collaborate with the LNP and analytical teams to assess mRNA quality following formulation, including mRNA integrity and characterization/troubleshooting of mRNA-lipid adduct formation.
Analyze, summarize, and communicate findings to team leadership and project teams.
Document work in electronic lab notebook and author project summaries as needed.
Provide scientific, project, and laboratory leadership to junior scientific staff. Lead by example with lab safety.

Qualifications/Experience

B.S., M.S., or Ph.D. in Molecular Biology, Biochemistry, Chemistry, Bioengineering, or a related field.
2-6+ years of biotech/pharma experience post-Ph.D., or equivalent industry experience for candidates with an M.S. or B.S.
Subject matter expertise in design, production, and analytical characterization of mRNA for gene or antigen therapy.
Ability to identify, troubleshoot, and solve issues associated with complex materials.
Strong organizational skills and attention to detail; collaborative, accountable, and an effective communicator.

Preferred Qualifications

Experience with RNA-driven innate immune activation.
Experience with in vitro cell culture and flow cytometry is a plus.
Hands-on experience with production and purification of IVT-produced mRNA.
Experience with lipid nanoparticle formulation and/or characterization of mRNA-LNP drug products, including process scale-up, is a plus.
Experience with IP-RP HPLC for analytical characterization.

Compensation and Benefits
The base salary for this role ranges from $120,000 to $160,000 and is determined based on a candidate’s skills, experience, and internal equity. In addition to a competitive base salary, Repertoire offers a broad range of benefits designed to attract, retain, and motivate top talent, including medical, dental, vision, and life insurance, flexible time off, a 401(k)-retirement plan, and short- and long-term incentive opportunities. Compensation and benefits are based on Repertoire’s good faith estimate at the time of publication and may be updated in the future.
Repertoire is committed to building an inclusive culture. Much as the power of the immune system lies in the diversity of T and B cells, we believe our best work comes from a diverse workforce—and we are committed to pursuing that in all facets of the work experience. Repertoire is proud to be an Equal Opportunity Employer.

Recruitment & Staffing Agencies: Repertoire Immune Medicines (“Repertoire”) does not accept unsolicited resumes from any source other than candidates. The submission of unsolicited resumes by recruitment or staffing agencies to Repertoire or its employees is strictly prohibited unless contacted directly by Repertoire’s internal Human Resources team. Any resume submitted by an agency in the absence of a signed agreement will automatically become the property of Repertoire, and Repertoire will not owe any referral or other fees with respect thereto.

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