Oligo Discovery Process Chemistry Principal Scientist

GSK•Cambridge, MA

3d•$121,275 - $202,125•Onsite

About The Position

The successful candidate will join GSK’s oligonucleotide synthesis lab as a process discovery chemist, bridging early discovery-stage chemistry with the process rigor needed to reliably deliver in vivo study material. This is a discovery lab that produces rodent- and NHP-scale API using an ÄKTA Oligosynt synthesizer. The focus is on developing and troubleshooting solid-phase oligonucleotide synthesis (SPOS) routes at milligram-to-gram scale, building out method development and chromatography/purification strategies, and ensuring those routes translate cleanly as programs move toward larger-scale synthesis. Areas of focus include ASOs, siRNA, SSO, and RNA editors, spanning routine and next-generation amidite chemistries, conjugates, and purification method development.

Requirements

PhD in chemistry, chemical biology, or a related field, with 2–4+ years of industry experience in oligonucleotide process chemistry, process discovery, or related synthesis/process roles.
Hands-on experience with solid-phase oligonucleotide synthesis (SPOS) at milligram-to-gram scale, including method development, chromatography, and purification strategies that support larger-scale synthesis.
General familiarity with mid-scale synthesizers, such as ÄKTA Oligosynt and Mermade12, ÄKTA Avant and Pure purification systems with Unicorn software, and LC/HRMS, UPLC, LC/MS analytics.
Expertise in oligonucleotide synthesis (SPOS) and biological familiarity with RNA therapeutics (e.g. ASO, siRNA, SSO, RNA Editors), with the ability to generate in vivo rodent- and NHP-scale API0.

Nice To Haves

Minimum PhD with 4+ years of experience in oligonucleotide process chemistry, process discovery, oligo chemistry, or related fields.
Direct experience generating in vivo study material (rodent and/or NHP scale) in a discovery or process development environment.
Experience translating discovery-stage synthesis routes into larger-scale synthesis and purification strategies.
Prior experience with scientific and professional mentorship and project management.
Team-focused with strong initiative and ability to troubleshoot challenges and implement new solutions.
Excellent written and verbal communication skills, attention to detail, organizational skills, and the ability to collaborate effectively with a team are required.
Experience with oligonucleotide conjugation chemistries is desirable but not required.
Sense of urgency, flexibility, independence and accountability.
Ability to communicate both verbally and in writing with all levels both inside and outside of the organization.
Maintain a high level of integrity while balancing multiple priorities and responsibilities.
Must be a committed team player prepared to work in and embrace a team-based culture.

Responsibilities

Lead process discovery for oligonucleotide therapeutics, developing and troubleshooting SPOS routes from milligram to gram scale for ASOs, siRNA, SSO, and RNA editors with routine and next-generation amidite chemistries.
Generate in vivo study material at rodent and NHP scale using an ÄKTA Oligosynt synthesizer, ensuring synthesis and purification strategies translate cleanly from discovery into larger-scale production.
Develop and optimize chromatography and purification strategies (e.g., IEX, RP, AEX) that scale from milligram discovery quantities through gram-scale campaigns.
Perform hands-on method development, establish oligo synthesis and purification workflows, and draft SOPs that bridge discovery chemistry and process/scale-up needs.
Serve as the oligo synthesis and process discovery SME for the team, representing process chemistry in various cross-matrix meetings.
Develop and maintain standard operating procedures (SOPs) for synthesis, processing, and purification to ensure high-quality, reproducible in vivo-grade material.
Partner with the oligo analytical and conjugate chemistry teams to ensure accountability and excellence in oligonucleotide and conjugate synthesis.
Collaborate and communicate across discovery, process, and analytical teams to build robust, scalable workflows and deliver on portfolio endpoints.