Senior Scientist, Oligonucleotide

CRISPR Therapeutics•Boston, MA

2d•$145,000 - $155,000•Onsite

About The Position

We are seeking a highly skilled and motivated Senior Oligonucleotide Scientist to join our non-viral delivery (NVD) technical development team. In this role, you will serve as a technical lead in the design, synthesis, purification and analysis of modified oligonucleotides. You will drive the innovation in chemical modifications, scale-up process development and optimizations to support our advancing pipelines from early-stage research and discovery through clinical development. The ideal candidate possesses deep expertise in solid-phase synthesis, state of the art purification techniques, and analytical characterization, combined with a proven track record of mentoring junior scientists, leading cross-functional projects.

Requirements

A Ph.D. in Organic Chemistry, Medicinal Chemistry or a closely related discipline with 4.5-8+ years of experience and minimum of 2 years industrial biopharma/biotech experience OR non-PhD with 12-15 years of progressive, relevant experience.
Deep understanding of phosphoramidite chemistry, protecting group strategies, and nucleotide modifications (e.g., 2'-OMe, 2'-F, phosphorothioates, locked nucleic acids).
Hands-on experience with automated oligonucleotide synthesizers (e.g., Cytiva ÄKTA Oligopilot, Mermade, etc.) and preparative purification systems.
Strong background in troubleshooting and interpreting mass spectrometry (LC-MS) data for complex macromolecules.

Nice To Haves

Familiarity with ICH guidelines and cGMP manufacturing environments is highly desirable.
Strong problem-solving skills and the ability to thrive in a fast-paced, matrixed environment.
Excellent written and verbal communication skills for presenting data to both technical and non-technical stakeholders.
Proven ability to lead projects and foster a collaborative team environment.

Responsibilities

Lead the design and execution of automated solid-phase synthesis of complex, highly modified oligonucleotides at various scales.
Develop and optimize robust purification processes using preparative RP-HPLC, IEX and SEC, as well TFF and lyophilization.
Oversee and perform comprehensive structural elucidation and purity assessments using LC-MS, MALDI-TOF, NMR, and capillary electrophoresis.
Drive the optimization of synthetic routes and cleavage/deprotection methodologies to improve yields, reduce impurities, and ensure scalable, reproducible processes.
Evaluate and implement novel chemical modifications, conjugation strategies (e.g., GalNAc, lipids, peptides), and delivery technologies to enhance oligonucleotide stability and potency.
Serve as the oligochemistry lead on multidisciplinary project teams.
Supervise, mentor, and train junior chemists and laboratory technicians.
Maintain meticulous laboratory notebooks, write SOPs, and contribute to regulatory filings.
Manage inventory of oligonucleotides testing articles as well as critical reagents and phosphoramidites for Oligo Synthesis and purification.
Analyze, interpret, and organize data to prepare experimental reports and communicate the results of the projects at internal and external meetings.