Senior / Principal Scientist:
Synthetic Chemistry (Oligonucleotide Medicines)

Pay: $100,000 – $180,000 per year
Location: Rockville, MD (on-site)

About Us:

Founded in 2017 by scientists from Harvard Medical School and UCSF, Autonomous Therapeutics is developing first-in-class nucleic acid medicines for difficult-to-treat infectious disease and oncology indications.

Our platform fuses synthetic biology, chemistry, and therapeutic engineering to achieve a simple goal: target-activated (precision) medicines that only activate in diseased cells. Imagine a chemotherapy that is programmed to avoid your healthy cells.

You would join a team of 25 PhD scientists and engineers across synthetic biology, synthetic chemistry, immunology, cell biology, in vivo biology, and AI in our 20,000 sq ft R&D facility outside Washington, D.C.

The Role:

A fundamental challenge for nucleic acid therapeutics is efficient and precision delivery outside of the liver. 

We are looking for an exceptional synthetic chemist to help develop the next generation of oligonucleotide medicines. 

This role focuses on solid-phase oligonucleotide synthesis, modified RNA/DNA chemistry, functionalized solid supports, on-column ligand installation, and SAR-driven linker/ligand optimization strategies.

You will play a leading role in designing, synthesizing, and characterizing novel extrahepatic oligonucleotide candidates, including modified oligos, ligand-conjugated oligos, functionalized supports, and delivery-enabling chemistries.

You will work closely with our in-house chemistry, formulation, cell biology, immunology, and in vivo teams to help translate new chemistries into preclinical therapeutic candidates.

This critical role reports directly to the Head of Oligonucleotide Chemistry and to the CEO.

About You:

You have a PhD in Chemistry, Chemical Biology, Materials Science or a related field and demonstrated expertise in ONE or more of:

Oligonucleotide Synthesis & Purification

Solid-phase synthesis, deprotection, purification, and characterization of RNA or DNA oligonucleotides, including siRNA, ASOs, or related modalities. Experience with backbone, sugar, base, and terminal modifications is highly valued.

Functionalized Solid Supports & On-Column Chemistry

Experience developing or using functionalized CPGs, synthesis supports, protected ligands, synthesis handles, or on-column conjugation strategies to install delivery ligands such as GalNAc, carbohydrates, peptides, lipids, polymers, or other targeting moieties.

Linker / Ligand Synthesis & Optimization

Design, synthesis, and SAR-driven optimization of oligonucleotide linkers and ligands that improve delivery, biodistribution, pharmacokinetics (PK), cellular uptake, or in vivo potency. Experience with established hepatic platforms such as GalNAc is highly valued as a foundation for extrahepatic delivery.

CMC, Scale-Up & CDMO Interface

Experience supporting oligonucleotide scale-up, process development, technology transfer, external CDMO management, and cGMP manufacturing.

Nice to Have (Not Required):

• Experience with LC-MS, HPLC, ion-exchange chromatography, reversed-phase chromatography, SEC, PAGE, or related methods to assess oligonucleotide purity, identity, yield, and product quality.

• Experience synthesizing or optimizing GalNAc, carbohydrate, peptide, lipid, polymer, or other ligand-conjugated oligonucleotides.

• Experience with cleavable and non-cleavable linker designs, including enzymatic, redox-sensitive, acid-labile, or other release strategies.

• Experience developing modified CPGs, phosphoramidites, activated esters, azides/alkynes, amines, thiols, or other handles for solid-phase or post-synthetic conjugation.

• Experience with formulation or particle engineering approaches relevant to nucleic acid therapeutics, including spray drying, lyophilization, dry-powder inhalation, or controlled release.

• Experience testing therapeutic candidate potency, biodistribution, safety, or efficacy in vitro or in vivo.

What You’ll Do:

• Design, synthesize, purify, and characterize novel oligonucleotide candidates and conjugates

• Develop and optimize solid-phase synthesis strategies for modified RNA/DNA oligonucleotides, ligand-conjugated oligos, and delivery-enabling chemistries.

• Develop or apply functionalized CPGs, synthesis supports, protected ligands, synthesis handles, and on-column conjugation strategies.

• Perform SAR-driven optimization of linker, ligand, and conjugate chemistries to improve synthesis efficiency, stability, biodistribution, pharmacokinetics, cellular uptake, and in vivo potency.

• Help establish internal workflows, quality standards, and troubleshooting approaches for oligonucleotide synthesis, purification, and characterization.

• Collaborate with formulation, cell biology, immunology, and in vivo teams to translate chemical designs into tested preclinical candidates.

• Work with external CDMOs and strategic partners to support scale-up, technology transfer, cGMP manufacturing, and clinical advancement.

• Mentor junior scientists and help grow the oligonucleotide chemistry team.

Why Join:

• Impact:
  Help develop first-in-class cancer and infectious disease medicines.

• Science:

  Work across synthetic chemistry, oligonucleotide medicines, synthetic biology, cancer biology, immunology, virology, formulation, and in vivo pharmacology.

• Skill Development: 

  Have the opportunity to learn biology and therapeutic development or cutting-edge AI. You’ll also be exposed to the business of a fast-paced startup.

• Compensation:
  Highly competitive salary and equity (stock option) packages.

• Benefits:

  • Health, dental, and vision insurance

  • 401(k) with employer matching

  • Paid time off

• Culture:

  Work alongside a highly collaborative team of scientists and engineers in a fast-moving biotech startup.

Hiring Info:

• Work Authorization:

  Candidates must be authorized to work in the United States.

• Merit-Based:

  Hiring decisions are based on merit, qualifications, and business needs. Autonomous Therapeutics is an Equal Opportunity Employer.