(Senior / Principal) Scientist, RNA Therapeutics

Capable Labs • San Francisco, CA

8d • Onsite

About The Position

We are a vibrant and intensely mission-driven team in San Francisco, comprising members from MIT, Harvard Medical School, Roche, ETH, and Dana-Farber. We value speed and rigor, coupled with excitement, drive, and a strong work ethic. In an early-stage environment, we value people who can bring clarity to open-ended problems, take ownership of the next steps, and follow through with energy. Capable Labs is a place for ambitious, high-integrity people who want to become dramatically better. You will be surrounded by people who care intensely about the work, get close feedback from the people making scientific and company-defining decisions, and have room to own increasingly important problems. We believe excellent work should be met with meaningful reward, ownership, and trust. Responsibility is earned through contribution, not title alone: anyone who demonstrates the judgment, rigor, and follow-through to move important work forward can earn meaningful scope. About the Role You will lead RNA-therapeutics programs from target biology and oligonucleotide design through chemistry selection, assay strategy, quality control, and in vivo validation. You will build coherent programs—not isolated sequences—by connecting mechanism, tissue, potency, durability, safety, and manufacturability to clear experimental decisions. This is a senior hands-on role with end-to-end scientific ownership.

Requirements

• Deep hands-on experience with RNA therapeutics, ASOs, siRNA, splice-switching oligonucleotides, RNA biology, nucleic-acid chemistry, pharmacology, or closely related work.
• The ability to reason from target biology to sequence and chemistry design to the assay readout that will validate or reject the approach.
• Experience designing and interpreting RNA-therapeutics assays at transcript, protein, pathway, cellular, or in vivo tissue level.
• Experience with methods such as qPCR, ddPCR, RNA-seq, western blot, ELISA, reporter assays, splice assays, cytokine panels, or tissue analysis is helpful; expertise in every method is not required.
• A rigorous, efficient, and resourceful approach to moving a program forward when sequences, assays, models, tissue analysis, or outside capabilities are missing.
• The ability to provide technical leadership while staying close to hands-on work and primary data.

Responsibilities

• Lead the design of ASOs, siRNAs, splice-switching oligonucleotides, gapmers, steric-blocking oligonucleotides, and other RNA-targeting molecules.
• Select oligonucleotide chemistries—including phosphorothioate backbones, 2′-MOE, 2′-OMe, LNA, cEt, PMO, and GalNAc or lipid conjugation—based on tissue, mechanism, potency, durability, safety, off-target risk, immune activation, and manufacturability.
• Develop sequence strategies for RNase H knockdown, splice modulation, translation blocking, miRNA inhibition, transcript stabilization, and other RNA-level mechanisms.
• Refine design rules involving GC content, RNA secondary structure, isoform selectivity, SNPs, conservation, and specificity.
• Source, synthesize, purify, and quality-control oligonucleotides using appropriate methods such as HPLC/UPLC, LC-MS, MALDI, UV quantification, PAGE, endotoxin/bioburden testing, and batch-level analytical tracking.
• Design and interpret assays for knockdown, splice correction, transcript and protein changes, pathway modulation, cell viability, immune activation, and in vivo tissue target engagement.
• Build the complete program package: target rationale, sequence set, chemistry plan, assay strategy, quality-control data, in vitro and in vivo results, failure modes, and next-step logic.
• Set technical direction, bring in outside expertise where useful, and remain directly involved in the experiments and data that determine program decisions.

Benefits

• Generous equity options
• Monthly wellness budget for training, supplements, coaching, recovery, or other tools that help you perform at your best.
• Medical, dental, and vision coverage options, with Capable covering 100% of the base policy.
• HSA, FSA, and 401K plans.
• Healthy dinners with the team are provided daily.
• Visa sponsorship where appropriate, including O-1, H-1B, J-1, TN, and other employment-based pathways.

What This Job Offers

• Job Type: Full-time
• Career Level: Senior
• Education Level: No Education Listed