Scientist I, Guide RNA Chemistry, Prime Medicine

Prime Medicine•Cambridge, MA

5d•Onsite

About The Position

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.

Requirements

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.
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.

Nice To Haves

Experience with enzymatic ligation, linker chemistry, or long RNA assembly is highly desirable but not required.

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.