Scientist I, Guide RNA Chemistry

Prime Medicine was founded to bring the promise of gene editing to patients. We use Prime Editing, a next-generation technology that can “search and replace” to restore normal genetic function almost anywhere in the genome. Prime Editing searches to find the precise place in the genome to edit and replaces the segment of faulty DNA with a correct copy of DNA. A single Prime Editor can correct the individual mutations found across patients, meaning Prime Editing can potentially address more than 90 percent of known disease-causing genetic mutations.

We envision a world where this technology can cure, halt, and ultimately prevent genetic diseases, providing lifelong benefit to patients. Prime Medicine offers the opportunity to shape the future of gene editing and transform how medicines are used to treat disease. Realizing the promise of Prime Editing requires a talented team with diversity of viewpoints and expertise. We’re building a group of dedicated, scientifically curious individuals who are passionate about helping patients live longer, healthier lives.

Position Overview

Prime Medicine is seeking a talented, highly motivated Scientist I with expertise in oligonucleotide chemistry to join our Guide Chemistry team. The successful candidate will have hands-on experience in long guide RNA synthesis, chemical deprotection, purification, desalting, and the implementation of novel chemistries to enhance guide RNA potency and quality, along with proficiency operating MerMade 12 and/or Dr. Oligo synthesizers for solid-phase RNA synthesis using phosphoramidite chemistry, followed by HPLC purification to support multiple discovery programs. This role requires a strong understanding of phosphoramidite chemistry, solid-phase oligonucleotide synthesis, linker chemistry, enzymatic ligation, and RNA purification techniques to enable guide RNA production for in vivo studies, preclinical development, and beyond.

The Scientist I will play a key role in troubleshooting technical challenges, improving throughput and process robustness, and ensuring reliable guide-RNA production for screening and animal studies. The individual will leverage scientific literature, collaborate with internal technical experts, and independently solve complex laboratory problems. Depending on experience, this individual may mentor co-ops, contractors, or junior scientists and will work closely with cross-functional teams including Analytical Development, Biology, Formulation, and Technical Development & Operations (TDO) to advance Prime Medicine's gene editing programs toward the clinic.

Key Responsibilities

• Design, plan, and execute complex laboratory experiments that support cross-functional research objectives.
• Demonstrate scientific creativity, technical excellence, and independent thinking in experimental design and execution.
• Synthesize chemically modified guide RNAs using MerMade 12 and/or Dr. Oligo automated synthesizers based on phosphoramidite solid-phase chemistry.
• Perform RNA cleavage, deprotection, desalting, purification, and sample preparation to deliver high-quality guide RNAs.
• Analyze crude and purified oligonucleotides using UPLC, LC-MS (Orbitrap), UV spectroscopy, and related analytical techniques to confirm identity, purity, and product quality.
• Troubleshoot synthesis, purification, and analytical challenges while maintaining laboratory instrumentation and ensuring operational efficiency.
• Drive continuous improvements in guide RNA synthesis workflows to increase throughput, robustness, reproducibility, and product quality.
• Collaborate closely with cross-functional teams, including Analytical Development, Biology, Formulation, and TDO, to deliver guide RNAs that meet aggressive project timelines.
• Maintain accurate electronic laboratory notebooks, experimental records, and data documentation.
• Present scientific findings at team meetings and contribute to technical discussions.
• Mentor and provide technical guidance to co-op students, contractors, or junior scientists as appropriate.

Qualifications

• PhD in Chemistry or related discipline with 0-2+ years OR MS with at 6+ years or BS with 8+ years of experience in an industry environment
• Hands-on experience with MerMade 12 and/or Dr. Oligo synthesizers for solid-phase oligonucleotide synthesis is strongly preferred.
• Demonstrated experience in phosphoramidite chemistry, RNA oligonucleotide synthesis, cleavage, deprotection, desalting, and HPLC purification.
• Experience producing chemically modified oligonucleotides in a high-throughput laboratory environment.
• Familiarity with analytical characterization techniques, including UPLC, LC-MS (Orbitrap), UV-Vis spectroscopy, and analytical data interpretation.
• Experience with enzymatic ligation, linker chemistry, or long RNA assembly is highly desirable but not required.
• Demonstrated ability to troubleshoot complex synthetic and purification challenges independently.
• Strong interpersonal and communication skills, with the ability to work effectively in a fast-paced, team-oriented environment and collaborate closely across cross-functional groups.
• Ability to mentor co-op students, contractors, or junior scientists.
• Highly self-motivated with a strong sense of ownership, urgency, and a "can-do" attitude.
• Excellent organizational, communication, and problem-solving skills with strong attention to detail.
• Passion for continuous learning, scientific innovation, and process improvement in a fast-paced research environment.