Senior or Principal Scientist: Analytical Chemistry (Oligonucleotide Therapeutics)

Autonomous Therapeutics; Indiana (PA); On-site; USD 120,000 - 160,000; Full time

Job summary

Autonomous Therapeutics in Rockville, MD seeks a senior synthetic chemist to advance next-generation oligonucleotide medicines beyond the liver, bridging solid-phase synthesis, RNA/DNA chemistries, and bioconjugation for delivery.

You will join a 25-strong chemistry and biology team at our MD facility, leveraging PhD-level expertise to design, synthesize, and optimize oligos, conjugates, and linkers for improved delivery and in vivo potency.

Qualifications

• PhD in Chemistry, Materials Science, or related field; strong record of accomplishment.
• 5+ years of relevant R&D experience, including PhD work.
• Experience with solid-phase synthesis of RNA/DNA oligonucleotides and modifications.
• Delivery conjugation chemistry experience; bioconjugates for improved delivery and in vivo potency.

Responsibilities

• Develop and optimize solid-phase synthesis of RNA/DNA oligonucleotides with desired backbone, sugar, base, and terminal modifications.
• Design, synthesize, and optimize bioconjugates to improve biodistribution, pharmacokinetics, and cellular uptake.
• Develop functionalized CPGs, ligands, linkers, and attachment handles for on-column or post-synthetic conjugation.
• Conduct LC-MS/HPLC analyses to assess identity, purity, and yield of oligonucleotide products.

Skills

Solid-phase synthesis

Delivery chemistry

Analytical chemistry

Bioconjugation

Synthesis planning

Education

PhD in Chemistry or related field

Tools

LC-MS

HPLC

Job description

The Position

We are seeking an exceptional synthetic chemist to help develop the next-generation of oligonucleotide medicines designed for delivery beyond the liver.

This role bridges solid-phase oligonucleotide synthesis, novel RNA and DNA chemistries, and delivery-enabling bioconjugation.

Depending on your expertise and interests, you may focus on synthesizing oligonucleotides, delivery ligands, or linkers or on developing conjugated therapeutic candidates.

You will join a growing team of 25 chemists, cell biologists, and in vivo biologists in our 20,000-square-foot R&D facility outside Washington, D.C.

About You

You have a PhD in Chemistry, Materials Science, or a related discipline and a strong record of scientific accomplishment.

Exceptional candidates may come from oligonucleotide chemistry, peptide chemistry, carbohydrate chemistry, polymer chemistry, bioconjugation chemistry, medicinal chemistry, chemical biology, or broader synthetic chemistry disciplines.

Solid-Phase Synthesis

Experience with 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. Substantial experience with solid-phase peptide synthesis or related synthetic platforms is also relevant, particularly for ligand synthesis, linker installation, or conjugate development.

Delivery & Bioconjugation

Experience designing, synthesizing, and optimizing bioconjugates to improve delivery, biodistribution, pharmacokinetics, cellular uptake, or in vivo potency. These may include conjugates incorporating oligonucleotides, peptides, antibodies, small molecules, carbohydrates, lipids, polymers, or other targeting moieties. Experience synthesizing or optimizing GalNAc, carbohydrate, peptide, lipid, polymer, or other ligand-conjugated candidates is highly valued.

Functionalization & Conjugation Chemistry

Experience developing or applying functionalized CPGs, synthesis supports, protected ligands, linkers, attachment handles, or on-column strategies to install delivery ligands onto oligonucleotides. Experience with solution-phase or post-synthetic conjugation, site-selective functionalization, orthogonal protecting groups, or bioorthogonal chemistry is also highly valued.

Analytical Chemistry

Experience with LC-MS and HPLC to assess candidate identity, purity, yield, and product quality. Experience with ion-exchange chromatography, reversed-phase chromatography, SEC, PAGE, or related analytical methods is also highly valued.

Nice to Have

• Experience supporting synthetic chemistry process development, scale-up, technology transfer, CDMO management, or cGMP manufacturing.


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


• Experience developing modified CPGs, phosphoramidites, activated esters, azide–alkyne click chemistry, amine- or thiol-reactive handles, or related approaches for solid-phase, on-column, 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 candidates in vitro or in vivo and using biological results to guide chemical design.

Education: PhD required

Experience: 5+ years of relevant R&D experience, including PhD work

Location: Rockville, MD (on-site)