Position Overview:

As a Principal/Senior Principal Scientist specializing in Oligonucleotide Chemistry, you will lead the research and development of novel conjugation strategies to enable efficient extrahepatic delivery of siRNA. You will design the synthetic chemistry and conjugation strategies as well as develop structure-activity relationship (SAR) for improved therapeutic profiles. This high-impact role requires a strong background in oligonucleotide chemistry, conjugation techniques, and preclinical research and development experience to enable our platform toward clinical milestones.

Key Responsibilities:

  • Oligonucleotide Chemistry and Conjugation: Design, synthesize (leveraging either internal or external resources where appropriate), and characterize conjugated oligonucleotide constructs for extrahepatic siRNA delivery, employing a range of chemistries, linkers, and targeting ligands.
  • Drive SAR Strategy: Plan and execute Structure-Activity Relationship studies to explore conjugation chemistries, linker and ligand designs, as well as the siRNA constructs. Form data driven strategies to refine iterative designs for enhanced potency, safety, pharmacokinetics, and biodistribution.
  • Cross-Functional Collaboration: Collaborate with interdisciplinary teams—biology, pharmacology, and formulation sciences—to evaluate the in vitro and in vivo performance of conjugated siRNAs. Provide guidance on conjugation strategies that align with biological and pharmacological requirements. 
  • Technology Evaluation: Stay current with emerging oligo conjugation technologies, novel chemical modifications, and industry best practices. Assess and implement new methods or reagents that could enhance extrahepatic oligonucleotide targeting, tissue biodistribution, and endosomal escape.
  • Data Analysis & Reporting: Conduct and interpret chemistry, biochemistry, and molecular biology characterizations to confirm molecular identity, purity, etc. Document results, generate technical reports, and present findings to project teams and senior leadership.
  • Innovation & IP Generation: Contribute to patent filing activities and participate in strategic decision-making for pipeline programs. Innovate novel conjugation designs and strategies, ensuring the intellectual property position remains strong.
  • Regulatory & Compliance: Ensure laboratory practices adhere to safety guidelines and regulatory standards. Contribute to the preparation of regulatory documentation required for preclinical and IND submissions.

 

Required Qualifications:

  • Ph.D. in Chemistry, Biochemistry, Chemical Biology, or a related field with at least 4-8 years of relevant experience focusing on oligonucleotide modification, conjugation, or siRNA delivery is highly desirable.
  • Versatile and diverse medicinal chemistry background with sound knowledge of biology and pharmacology with the ability to articulate chemistry to biologists and drive iterative SAR activities.
  • Strong background in nucleic acid chemistry, including solid-phase oligonucleotide synthesis and various conjugation techniques (e.g., click chemistry, NHS ester coupling, hydrazone, disulfide linkers).
  • Hands-on experience with advanced analytical instrumentation (e.g., NMR, IR, LC-MS, HPLC) for characterizing oligonucleotide conjugates.
  • Demonstrated expertise in designing and executing SAR studies to optimize oligo chemical modifications, linkers, and conjugation strategies.
  • Experience with siRNA or antisense oligonucleotide therapeutics optimization from hit to lead and a solid understanding of the factors influencing extrahepatic delivery (e.g., PK, target tissue tropism, endosomal escape) is a plus.
  • Proven ability to work in interdisciplinary teams and communicate findings effectively.
  • Strong organizational, problem-solving, and data interpretation skills.
  • Ability to manage multiple projects simultaneously in a fast-paced, evolving startup environment.
  • Innovative mindset with a passion for learning and applying new technologies.

 

Salary Ranges:

  • Principal Scientist: $135,000 to $180,000
  • Senior Principal Scientist:  $158,000 to $210,000

 

Company Overview:

Moonwalk Biosciences is pioneering a new class of precision epigenetic medicines. Its novel platform technology provides a complete view of the epigenome in health and disease, with the most advanced AI prediction of epigenetic targets, and the broadest set of epigenetic engineering tools. Moonwalk was Co-founded by Alex Aravanis, M.D., Ph.D., former CTO of Illumina, world-renowned scientist Feng Zhang, Ph.D. of the Broad Institute of MIT and Harvard, and a distinguished set of industry leaders and company builders. It has raised $57 million led by Alpha Wave Ventures, and joined by other leading life sciences investors ARCH Venture Partners, Future Ventures, GV, Khosla Ventures and YK Bioventures.

Equal Opportunity Employer:

Moonwalk Biosciences provides equal employment opportunities to all employees and applicants for employment and prohibits discrimination and harassment of any type without regard to race, color, religion, age, sex, national origin, disability status, genetics, protected veteran status, sexual orientation, gender identity or expression, or any other characteristic protected by federal, state or local laws. 

This policy applies to all terms and conditions of employment, including recruiting, hiring, placement, promotion, termination, layoff, recall, transfer, leaves of absence, compensation and training.