Research Associate II, Oligonucleotide Synthesis

CRISPR Therapeutics•South Boston, MA

16h•Onsite

About The Position

CRISPR Therapeutics is seeking a hands-on Research Associate II to support oligonucleotide synthesis, purification, and conjugation for gene-editing and targeted-delivery programs. The role involves running solid-phase oligonucleotide synthesis on automated platforms, purifying and characterizing crude material to research-grade specifications, and preparing small molecule–oligonucleotide and antibody–oligonucleotide conjugates. This is a bench-intensive position in a fast-moving discovery chemistry group. Working under senior scientists, the associate will execute defined experimental plans, progressively take ownership of syntheses, purification campaigns, and conjugation reactions, and deliver well-documented material on time to in vitro and in vivo study teams. CRISPR Therapeutics is a biopharmaceutical company developing gene-based medicines for serious human diseases. Its pipeline spans hemoglobinopathies, cardiovascular, autoimmune, oncology, regenerative medicine, and rare diseases. The company also develops SyNTase™, a gene-editing platform, and has strategic collaborations including with Vertex Pharmaceuticals. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with U.S. R&D operations in Boston and San Francisco. The role is fully on-site. The listed base pay range is $85,000 to $92,000, plus bonus, equity, and benefits.

Requirements

BS in Chemistry, Biochemistry, Chemical Biology, or a related discipline with 2+ years of relevant laboratory experience; or MS in a related discipline with 0–2+ years of experience.
Hands-on experience with solid-phase oligonucleotide synthesis on an automated synthesizer, including cleavage, deprotection, and workup.
Demonstrated experience with preparative HPLC purification and interpretation of analytical HPLC or LC-MS data.
Practical experience with at least one bioconjugation chemistry, such as NHS ester, maleimide–thiol, or click chemistry, applied to oligonucleotides, peptides, or proteins.
Strong general wet-chemistry experience, including accurate weighing, solution preparation, air- and moisture-sensitive handling, and anhydrous techniques.
Meticulous documentation habits and comfort working in an electronic lab notebook.
Ability to manage multiple parallel experiments and deliver against timelines in a fast-paced environment.

Nice To Haves

Experience synthesizing chemically modified siRNA, ASO, or guide RNA with phosphorothioate and 2′-modified nucleotides.
Experience preparing GalNAc, lipid, or peptide conjugates for targeted nucleic acid delivery.
Experience with antibody handling and antibody–drug or antibody–oligonucleotide conjugate preparation and characterization, including DAR determination.
Familiarity with protein purification platforms such as FPLC, SEC, HIC, and TFF.
Experience with LC-MS deconvolution software and chromatography data systems such as Empower, Chromeleon, or Unicorn.
Exposure to design of experiments or structured screening approaches for reaction optimization.
Experience supporting material transfer to external vendors or CDMOs.

Responsibilities

Execute phosphoramidite-based solid-phase synthesis of chemically modified RNA and DNA on automated synthesizers at micromole to millimole scales.
Incorporate modified building blocks, including 2′-OMe and 2′-F nucleotides, phosphorothioate and other backbone modifications, and 5′/3′ functional handles for conjugation.
Perform cleavage from support, base and 2′-silyl deprotection, desalting, and lyophilization using established protocols.
Prepare amidite and reagent solutions; maintain synthesizer uptime through routine maintenance and troubleshooting; manage consumable and raw-material inventory.
Purify crude oligonucleotides by RP-HPLC and IEX-HPLC; pool, desalt, concentrate, and formulate final material to target concentration and buffer.
Assess identity and purity using LC-MS, UPLC, and UV quantification, and interpret chromatograms and deconvoluted mass data.
Prepare small molecule–oligonucleotide conjugates, including GalNAc, lipid, and peptide conjugates, and support antibody–oligonucleotide conjugation using standard bioconjugation chemistries.
Purify conjugates by chromatography and filtration; assess purity, conjugation efficiency, and drug-to-antibody ratio.
Conduct small-scale reaction-condition screens and summarize results for the team.
Maintain complete, contemporaneous electronic lab notebook records and accurate sample registration and inventory in compound and reagent management systems.
Analyze and present data clearly at team and project meetings.
Follow EHS requirements, including safe handling of organic solvents and reactive reagents, proper waste disposal, and correct use of fume hoods and personal protective equipment.