Group Leader, Antibody-Oligonucleotide Conjugates (Extrahepatic Delivery)

A*STAR RESEARCH ENTITIES; Singapore; On-site; SGD 180,000 - 270,000; Full time

Benefits offered by this job

Competitive compensation

Long-term career growth

Global opportunities

Job summary

Nucleic Acid Therapeutics Initiative (NATi) at A*STAR invites applications for a Group Leader to build and lead an interdisciplinary team developing antibody-oligonucleotide conjugates (AOCs) for extrahepatic delivery in Singapore.

You will own the scientific strategy, establish platform capabilities, and partner with oligonucleotide chemistry, DMPK, and bioanalytics to advance assets toward development, with a global recruitment and competitive compensation.

Qualifications

• PhD in a relevant field.
• 8+ years as Sr. Scientist or 12+ years as Principal Scientist in pharma/biotech.
• Proven antibody discovery/engineering and bioconjugation ownership.

Responsibilities

• Define AOC design principles for extrahepatic delivery and payload selection.
• Drive program strategy, milestones, and decision frameworks.
• Lead multi-disciplinary project teams and governance reviews.
• Oversee antigen/epitope strategy and antibody discovery via display technologies.
• Engineer antibodies for affinity, internalization, stability, and developability workflows.
• Own bioconjugation strategy and define oligo formats in collaboration with chemists.
• Establish analytical methods for DAR, purity, and stability; supervise purification and analytics workflows.
• Develop in vitro assays for binding, internalization, and oligo activity; drive in vivo PK/PD studies.

Skills

Scientific leadership

Cross-functional collaboration

Project management

Communication

Education

PhD in Protein Engineering/related field

Job description

About NATi:

The Nucleic Acid Therapeutics Initiative (NATi), hosted by A*STAR, is Singapore's national platform dedicated to advancing RNA-based medicines and revolutionizing drug and vaccine development. NATi's mission is to establish Singapore as a globally recognized hub of excellence in nucleic acid therapeutics research, clinical translation, and commercialization.

NATi focuses on key RNA modalities such as antisense oligonucleotides (ASOs), small interfering RNA (siRNA), and messenger RNA (mRNA). To drive this vision, NATi is building a biotech-like translational engine focused on asset and technology development spanning discovery to clinical development.

We are actively seeking passionate and committed RNA scientists with deep translational expertise to join us in advancing the next generation of RNA-based therapeutics.

Position Overview

We seek a highly innovative and results-driven Group Leader to build and lead an interdisciplinary team developing antibody-oligonucleotide conjugates (AOCs) for extrahepatic delivery. This role will integrate antibody discovery and engineering with linker chemistry, oligonucleotide conjugation, and fit-for-purpose bioanalytical and functional validation to enable asset generation beyond established hepatic indications. The successful candidate will own the scientific strategy and execution for the AOC platform, build an efficient group, establish platform capabilities (e.g., automation, conjugation, analytics, in vitro assays), and partner closely with oligonucleotide chemistry, DMPK, and bioanalytics teams.

Key Responsibilities

1) Scientific Leadership & Program Ownership

• 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.

2) Antibody Discovery, Engineering & Developability

• 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 selectionInternalization/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

3) Linker Chemistry & Oligo Conjugation Platform

• 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 circulationControlled release (if/as applicable)Compatibility with antibody and oligo chemistryScalability and CMC readiness
• Establish analytical methods to quantify DAR, positional heterogeneity, purity, and stability (e.g., LC-MS, SEC, CE-SDS, HIC, UV/fluorescence, ion exchange, oligo integrity assays) plus hands-on experience with multiscale purification and analytical characterization instruments.

4) Functional Validation Readouts

• 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)
• Drive in vivo PK/PD and biodistribution studies in relevant models in close partnership with pharmacology team

5) Cross-Functional Partnering

• Collaborate with DMPK to establish AOC-specific ADME understanding (e.g., deconjugation, metabolite profiling, clearance mechanisms)
• Partner with Bioanalytics to set up assays for intact conjugate, total antibody, free oligo, and catabolites.
• Work with CMC/process development for scale-up readiness, control strategy, and quality attributes (CQAs) relevant to AOCs

6) People Leadership & Capability Building

• Recruit, mentor, and lead a team across protein science, conjugation chemistry, and biology
• Establish best practices for experimental design, documentation, and reproducibility; cultivate a culture of scientific excellence with a sense of urgency
• Identify and manage CRO partnerships to accelerate program timelines; Lead strategic collaborations as needed
• Lead innovation in AOC engineering to expand NATi's intellectual property (IP) portfolio.
• Coordinate technical documentation and patent filings in collaboration with legal and scientific teams.
• Prepare appropriate summary reports and presentations to update NATi leadership and stakeholders.

Qualifications & Experience

• 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.
• A dependable contributor to cross-functional teams who embraces a collaborative culture while demonstrating the autonomy/initiative to deliver on assigned scientific and operational responsibilities.
• Excellent organizational, interpersonal, and verbal/written communication skills.

Global Recruitment & Competitive Compensation

NATi is conducting a global search for top-tier talent in RNA therapeutics. We welcome applications from leading pharmaceuticals scientists and biotech innovators worldwide.

This role provides a highly competitive compensation package aligned with global industry standards, including attractive benefits and long-term career growth opportunities within Singapore's thriving biomedical innovation ecosystem. Join us in shaping the future of RNA-based medicines and establishing Singapore as a world-class hub for nucleic acid therapeutics.

The above eligibility criteria are not exhaustive. A*STAR may include additional selection criteria based on its prevailing recruitment policies. These policies may be amended from time to time without notice. We regret that only shortlisted candidates will be notified.