Research Associate II, Oligonucleotide Synthesis

Job Description:

Company Overview

Founded over a decade ago, CRISPR Therapeutics is a leading biopharmaceutical company focused on developing transformative gene-based medicines for serious human diseases. The Company has evolved from a pioneering research-stage organization into an industry leader, marking a historic milestone with the approval of CASGEVY® (exagamglogene autotemcel [exa-cel]), the world’s first CRISPR-based therapy, approved for eligible patients with sickle cell disease and transfusion-dependent beta thalassemia. CRISPR Therapeutics is advancing a broad and diversified pipeline across hemoglobinopathies, cardiovascular, autoimmune, oncology, regenerative medicine and rare diseases. The Company continues to expand its leadership in gene editing through the development of SyNTase™ editing, a novel and proprietary gene-editing platform designed to enable precise, efficient, and scalable gene correction. To accelerate and expand its impact, CRISPR Therapeutics has established strategic collaborations with leading biopharmaceutical partners, including Vertex Pharmaceuticals. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Boston, Massachusetts and San Francisco, California.

Position Summary

We are seeking a hands-on Research Associate II to support the synthesis, purification, and conjugation of oligonucleotides for our gene editing and targeted delivery programs. In this role you will run solid-phase oligonucleotide synthesis on automated platforms, purify and characterize crude material to research-grade specifications, and prepare small molecule–oligonucleotide and antibody–oligonucleotide conjugates that enable tissue-targeted delivery. This is a bench-intensive position within a fast-moving discovery chemistry group. You will work under the guidance of senior scientists to execute defined experimental plans with high quality and throughput, while progressively taking ownership of your own syntheses, purification campaigns, and conjugation reactions. Success in this role means reliable, well-documented material delivered on time to in vitro and in vivo study teams.

Responsibilities

Oligonucleotide Synthesis

• Solid-phase synthesis: Execute phosphoramidite-based synthesis of chemically modified RNA/DNA on automated synthesizers at scales from micromole to millimole.

• Modified chemistries: Incorporate chemically modified building blocks (i.e. 2′-OMe, 2′-F) phosphorothioate and other backbone modifications, and 5′/3′ functional handles for downstream conjugation.

• Cleavage and deprotection: Perform cleavage from support, base and 2′-silyl deprotection, desalting, and lyophilization using established protocols.

• Reagent and instrument readiness: Prepare amidite and reagent solutions, maintain synthesizer uptime through routine maintenance and troubleshooting, and manage consumable and raw material inventory.

Purification and Analysis

• Preparative purification: Purify crude oligonucleotides by RP-HPLC, IEX-HPLC; pool, desalt, concentrate, and formulate final material to target concentration and buffer.

• Analytical characterization: Assess identity and purity by LC-MS, UPLC, and UV quantification; interpret chromatograms and deconvoluted mass data

Small Molecule and Antibody Conjugation

• Conjugate preparation: Prepare small molecule–oligonucleotide conjugates, such as GalNAc, lipid, and peptide conjugates, and support preparation of antibody–oligonucleotide conjugates using standard bioconjugation chemistries.

• Purification and characterization: Purify conjugates by chromatography and filtration, and assess purity, conjugation efficiency, and drug-to-antibody ratio.

• Reaction optimization: Run small-scale screens of reaction conditions and summarize results for the team.

Documentation and Collaboration

• Record keeping: Maintain complete, contemporaneous electronic lab notebook records and accurate sample registration and inventory in the compound and reagent management systems.

• Data communication: Analyze and present data clearly at team and project meetings.

• Safety and compliance: Work in accordance with all EHS requirements, including safe handling of organic solvents and reactive reagents, proper waste disposal, and correct use of fume hoods and personal protective equipment.

Minimum Qualifications

• 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.

Preferred Qualifications

• 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.

Competencies

• Collaborative – Openness, One Team
• Undaunted – Fearless, Can-do attitude
• Results Orientation – Delivering progress toward our mission. Sense of urgency in solving problems.
• Entrepreneurial Spirit – Proactive. Ownership mindset.

​Due to the nature of their work, our manufacturing and lab-based positions are located fully on-site.  

Research Associate II: Base pay range of $85,000 to $92,000+ bonus, equity and benefits

CRISPR Therapeutics, Inc. is committed to equal employment opportunity and non-discrimination for all employees and qualified applicants without regard to a person's race, color, gender, age, religion, national origin, ancestry, disability, veteran status, genetic information, sexual orientation or any characteristic protected under applicable law.

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