(Senior / Principal) Scientist, RNA Therapeutics

Capable Labs; San Francisco (CA); On-site; USD 180,000 - 250,000; Full time

Benefits offered by this job

Wellness budget

Healthcare coverage

401K

Visa sponsorship

Daily dinners

Job summary

Capable Labs in San Francisco seeks a senior leader to drive RNA-therapeutics programs from target biology through in vivo validation. You will own end-to-end decisions linking mechanism, tissue, potency, durability, safety, and manufacturability.

You will set technical direction, stay hands-on with data, and collaborate with a diverse team to translate science into impactful therapies. This is a senior, hands-on role requiring deep expertise in ASOs, siRNA, and oligonucleotide chemistry, with a

Qualifications

• Deep hands-on experience with RNA therapeutics, ASOs, siRNA, splice-switching oligonucleotides, RNA biology, nucleic-acid chemistry, pharmacology, or closely related work.
• 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.

Skills

RNA therapeutics

ASOs

siRNA

oligonucleotides

RNA biology

nucleic-acid chemistry

pharmacology

Tools

qPCR

RNA-seq

Western blot

Job description

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.

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.

Ideal Qualifications

• 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.

Pay & Benefits

• In addition to the posted salary range, we offer generous equity options.
• Compensation will depend on the skills, experience, and scope of impact you bring. If your background, experience, or compensation needs fall outside this range, we are still open to a conversation based on the scope and impact you could bring.
• $500+ monthly wellness budget for training, supplements, coaching, recovery, or other tools that help you perform at your best.
• Healthcare: We offer a broad range of medical, dental, and vision coverage options, with Capable covering 100% of the base policy.
• You will also have access to HSA, FSA, and 401K plans.
• Healthy dinners with the team are provided daily.
• We support visa sponsorship where appropriate, including O-1, H-1B, J-1, TN, and other employment‑based pathways. Our team is already international, with members from Canada, Pakistan, Germany, Austria, Switzerland, China, India, and the United States.

Equal Opportunity

Capable is an Equal Opportunity Employer; employment with Capable is governed on the basis of merit, competence and qualifications and will not be influenced in any manner by race, color, religion, gender, national origin/ethnicity, veteran status, disability status, age, sexual orientation, gender identity, marital status, mental or physical disability or any other legally protected status.