BS in Chemistry, Biochemistry, Chemical Biology, or related field with 2+ years of lab experience; or MS with 0-2+ years.
Hands-on experience with solid-phase oligonucleotide synthesis on automated synthesizers.
Demonstrated experience with preparative HPLC purification and analytical data interpretation.
Practical experience with bioconjugation chemistries applied to oligonucleotides, peptides, or proteins.
Strong general wet-chemistry skills, including accurate weighing and solution preparation.
Meticulous documentation habits and proficiency in electronic lab notebooks.
Ability to manage multiple experiments in a fast-paced environment.
Responsibilities
Execute solid-phase oligonucleotide synthesis using automated platforms.
Incorporate chemically modified building blocks for downstream conjugation.
Perform cleavage, deprotection, and purification of oligonucleotides.
Maintain reagent and instrument readiness through routine maintenance.
Purify crude oligonucleotides using RP-HPLC and IEX-HPLC.
Prepare small molecule-oligonucleotide conjugates and support antibody conjugate preparation.
Maintain accurate records and communicate data effectively at team meetings.
Benefits
Comprehensive health insurance plans.
Retirement savings plan with company match.
Generous paid time off and holiday schedule.
Opportunities for professional development and training.
Collaborative and innovative work environment.
Full Job Description
Job Description:
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.
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
About CRISPR Therapeutics AG
CRISPR Therapeutics AG, a gene editing company, focuses on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 gene-editing platform. The company develops its products through in-house research programs and partnerships with biopharmaceutical companies and academic researchers. Its lead product candidate is CTX001, an ex vivo CRISPR gene-edited therapy for treating patients suffering from transfusion-dependent beta thalassemia or severe sickle cell disease in which a patient's hematopoietic stem cells are engineered to produce high levels of fetal hemoglobin in red blood cells. The company was formerly known as Inception Genomics AG and changed its name to CRISPR Therapeutics AG in April 2014. CRISPR Therapeutics AG was founded in 2013 and is headquartered in Zug, Switzerland.
