Scientist I/II, Nucleic Acid Chemistry

Alloy Therapeutics•Waltham, MA

1d•$126,000 - $144,000•Onsite

About The Position

We are Alloy Therapeutics—a biotechnology ecosystem company empowering the global scientific community to make better medicines together. Through a community of partners, we democratize access to pre-competitive tools, technologies, services, and company creation capabilities that are foundational for discovering and developing therapeutic biologics. The company facilitates affordable, non-exclusive access to the entire drug discovery community from academic scientists, small and medium biotech, to the largest biopharma. At Alloy, we believe our industry should compete on getting the best drugs to patients as quickly as possible, not exclusive access to the best platforms. As a reflection of our relentless commitment to the scientific community, we reinvest 100% of our revenue in innovation and access to innovation. MAY THE BEST DRUG WIN. Alloy is headquartered in Waltham, MA with additional labs in Cambridge, UK; Basel, Switzerland, and Athens, GA. Successful members thrive in our shared culture of accountability, deliberate trust, and open communication. As a team we aspire to work together to exceed expectations and collectively contribute across the global organization to always maintain our nimble, startup culture. This is an on-site and full-time position in Waltham, MA. At Alloy, we have an ethos of “Mentorship-By-Apprenticeship” in all of our positions. We strive to have workers in the office when needed to interact organically and face-to-face. Of course, as a lab-based operation, our cells and animals grow 7 days a week, 365 days per year. We respect and value our colleagues for their hard work that requires them to be in the lab every day. We ask our people who have more flexible accommodations, like this position, to appreciate their colleagues who have less flexibility. We are all one team! The Alloy Genetic Medicines group is innovating a novel RNA-based drug discovery platform, namely “AntiClastic”, spanning the fields of antisense therapeutics to immunomodulating therapeutics. This technology platform was launched by Alloy in 2023 after exclusively licensing its underlying intellectual property which implements a novel spatial conformation of the oligonucleotide developed by Sudhir Agrawal of Arnay Sciences. The team works closely with external partners to discover and develop AntiClastic RNA medicines. This position reports to the Head of Nucleic Acid Chemistry. We are seeking a detail-oriented Nucleic Acid Chemistry Scientist to join our growing Nucleic Acid Chemistry team supporting the CMC development of oligonucleotides, mRNA, pDNA templates, and antibody-oligonucleotide conjugates (AOCs). The successful candidate will bring strong hands-on expertise in synthesis and purification of nucleic acids, as well as HPLC and LC-MS analytics for RNA, DNA, and nucleic acid medicines. You will have a proven track record of developing, documenting, qualifying, and troubleshooting analytical methods and production processes in a fast-paced industrial environment. This role also requires experience working with and managing Contract Research Organizations (CROs), and developing/synthesizing reference materials to enable method development and program progression. This role may be filled at Scientist I or Scientist II depending on experience and demonstrated level of independence.

Requirements

Ph.D. in Analytical Chemistry, Biochemistry, Molecular Biology, or related field with 2–5 years of industry experience in nucleic acid synthesis or analytical development.
Hands-on experience in pDNA, mRNA, and oligonucleotide production: Including microbial fermentation, pDNA purification, linearization, and in vitro transcription (IVT), solid-phase synthesis, & lyophilization.
Extensive hands-on experience with HPLC/UPLC and LC-MS applied to mRNA, pDNA, oligonucleotides, and/or oligonucleotide conjugates.
Demonstrated success developing and qualifying analytical methods for nucleic acids (e.g., Capillary Electrophoresis/Fragment Analyzer for mRNA integrity).
Experience developing, synthesizing/sourcing, characterizing, and maintaining reference materials/standards.
Proven experience working with and managing CRO and/or CDMO partners.
Strong understanding of nucleic acid challenges (e.g., RNase-free handling, secondary structures, ion-pairing reagents, sequence variants, and conjugation heterogeneity).

Nice To Haves

Experience with antibody-oligonucleotide conjugates (AOCs) and LNP-formulated mRNA.
Familiarity with GMP/GLP environments and regulatory expectations for method lifecycle management.
Hands-on knowledge of complementary techniques (e.g., qPCR/ddPCR, SEC-MALS, and biophysical assays).

Responsibilities

pDNA Production: Execute microbial fermentation (E. coli) for plasmid DNA amplification; perform harvesting, lysis, and purification of pDNA.
Linearization: Perform enzymatic restriction digests to linearize pDNA templates for downstream transcription.
mRNA Synthesis: Lead in vitro transcription (IVT) reactions to produce mRNA, including enzymatic capping (Cap 1) and poly-adenylation.
Oligonucleotide: Execute procedures to synthesize oligonucleotides.
Purification: Utilize TFF (Tangential Flow Filtration) and chromatography (IEX, HIC, or Affinity) to purify intermediates and finished products from process-related impurities.
Develop, optimize, document, qualify, and transfer phase-appropriate analytical methods to support CMC activities for oligonucleotides, mRNA, pDNA, and AOCs.
Design fit-for-purpose methods for identity, purity, integrity, potency/assay, and stability, including forced-degradation studies.
Lead method qualification/verification activities for nucleic acid CQAs (e.g., product related purity, drug antibody ratios, mRNA capping efficiency, poly-A tail length, and residual template DNA).
Execute and interpret analyses using HPLC/UPLC modalities (e.g., IPRP, AE, IEX, HILIC, SEC).
Perform and interpret LC-MS analyses for intact oligos, mRNA mapping, sequence confirmation, impurity ID, and conjugate characterization.
Independently troubleshoot instrument and method issues, ensuring data integrity and project continuity.
Develop, qualify, and maintain analytical reference materials (e.g., standards, system suitability controls, impurity markers) to support method development, stability programs, and release testing.
Coordinate and/or perform internal synthesis (chemical or enzymatic) of oligonucleotide and mRNA reference materials and related controls.
Work effectively with and manage CRO/CDMO partners executing analytical studies, method development, or mRNA/pDNA manufacturing.
Author, review, and approve CRO protocols, reports, data packages, and method documentation.
Document experiments in real time with excellent attention to detail in electronic lab notebooks.
Support regulatory-compliant documentation for IND/BLA/MAA filings and respond to technical inquiries.

Benefits

Competitive base and equity compensation commensurate with level of experience and independence
401(k) company match
Generous personal and family medical, dental and vision benefits with 100% of premiums and deductibles covered
Company-paid disability (STD, LTD) and life insurance
Paid parental leave
Family planning support up to $45,000 (e.g., IVF/PGT, adoption, surrogacy, egg retrieval)
Unlimited PTO (paid time off) and flexible schedules
Annual stipend for continuing education with commitment to your career through individualized professional development plan
Wellness and Extensive Employee Assistance Program (EAP) including resources for mental wellness

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