A*STAR

Group Leader, Antibody-Oligonucleotide Conjugates (Extrahepatic Delivery)

A*STAR
ResearchSingaporeOnsitePosted 16 hours ago

About the role

AI summarised

Senior R&D leader responsible for building and directing an interdisciplinary team to develop antibody-oligonucleotide conjugates (AOCs) for extrahepatic delivery. The role spans scientific strategy, antibody discovery and engineering, linker chemistry, oligonucleotide conjugation, bioanalytical method development, and cross-functional collaboration to advance RNA therapeutics from discovery toward clinical development.

ResearchOnsite

Key Responsibilities

  • Define AOC design principles for extrahepatic delivery (i.e., target selection, tissue/cell specificity, internalization, trafficking, endosomal escape strategies, payload selection, etc.)
  • Drive program strategy, milestones, and decision-making frameworks (e.g., experimental plan, MOA validation, translation plan, developability risk)
  • Lead multi-disciplinary project teams and represent AOC programs in governance forums and senior leadership reviews
  • Guide antigen and epitope strategy for extrahepatic tissue targeting (e.g., muscle, adipose tissue, immune cells)
  • Oversee generation, screening, and prioritization of antibodies via different display technologies (e.g., phage/yeast display, hybridoma, or computational design) using a balanced combination of internal capability and external CROs
  • Engineer antibodies for: Affinity/avidity optimization, cross-reactivity, and species selection Internalization/trafficking (recycling vs. degradative pathways) Biophysical stability (aggregation, viscosity), PTMs, and manufacturability
  • Establish developability workflows (e.g., expression, purification, stability, aggregation, poly-specificity, immunogenicity risk screening) using a balanced combination of internal capability and external CROs
  • Own the bioconjugation strategy (site-specific vs. stochastic; cysteine/lysine conjugation, enzymatic conjugation, non-natural amino acids, glycan remodeling, click chemistry, etc.)
  • Partner with oligo chemists to define oligo formats (siRNA, ASO, splice-switching oligos, etc.), chemical modifications, and conjugation handles
  • Design and optimize linkers for: Stability in systemic circulation Controlled release (if/as applicable) Compatibility with antibody and oligo chemistry Scalability and CMC readiness
  • Develop and oversee in vitro assays to confirm: Binding and internalization (e.g., flow cytometry, microscopy, ligand competition) Intracellular trafficking/endosomal escape proxies Oligo activity (e.g., knockdown/splice modulation/qPCR/NGS readouts)

Requirements

  • A doctorate degree in Protein Engineering, Chemical Biology, Bioconjugation Chemistry, Organic/Medicinal Chemistry, or a related field
  • A minimum of +8 (Sr. Scientist) or +12 (Principal Scientist) years of relevant experience in pharmaceutical or biotech organizations
  • Demonstrated track record in antibody discovery/engineering and bioconjugation with clear ownership of programs advancing toward development
  • Hands-on experience with conjugation design, linker selection, and analytical characterization of conjugates (AOCs, ADCs, or related conjugate modalities)
  • Proven ability to lead cross-functional teams, set strategy, and deliver milestones in a matrix environment
  • Demonstrated innovation through IP, publications, IND filings, or other public disclosures
  • Excellent organizational, interpersonal, and verbal/written communication skills