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 revolutionising drug and vaccine development. NATi's mission is to establish Singapore as a globally recognised hub of excellence in nucleic acid therapeutics research, clinical translation, and commercialisation.
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 individuals with deep translational expertise to join us in advancing the next generation of RNA-based therapeutics.

Position Summary

We are seeking an accomplished scientific leader with deep expertise in skeletal muscle biology, preclinical pharmacology and targeted drug delivery to establish and lead NATi's muscle-targeted oligonucleotide therapeutics capability.

The initial mandate is to establish proof-of-concept for productive oligonucleotide delivery to skeletal muscle using antibody-oligonucleotide conjugates (AOCs) and alternative targeting approaches, including peptide, lipid and small-molecule conjugates. The successful candidate will leverage expertise in skeletal muscle biology, fibre and cellular heterogeneity, membrane receptor biology, receptor-mediated internalisation and intracellular trafficking to identify and validate cell-surface receptors and targeting strategies that enable selective and pharmacologically meaningful oligonucleotide delivery.

The Group Leader will establish the biological strategy, experimental systems and quantitative evaluation cascade to progress targeting approaches from receptor identification and validation through cellular uptake, intracellular trafficking, tissue biodistribution, target engagement, functional knockdown and in vivo proof-of-concept. This will require close collaboration with antibody engineering, oligonucleotide chemistry and conjugation, DMPK, bioanalytics and other platform teams.

Following successful demonstration of muscle delivery feasibility, the role will expand to establish a broader skeletal muscle therapeutic discovery capability, integrating human genetics, functional genomics, disease biology and experimental pharmacology to identify and validate novel therapeutic targets and build a differentiated pipeline of muscle-targeted oligonucleotide therapeutics for cardiometabolic and muscle-associated diseases.

The candidate will build and lead a multidisciplinary team spanning skeletal muscle biology, receptor and delivery biology, cellular pharmacology, target validation and in vivo pharmacology, while establishing internal capabilities and leveraging external CRO partnerships.

Job Description

Skeletal Muscle Biology & Targeting Strategy

• Provide scientific leadership in skeletal muscle biology, including muscle fibre composition and heterogeneity, cellular populations, muscle metabolism, physiology and disease-associated changes.
• Develop strategies to identify and prioritise cell-surface receptors and uptake mechanisms suitable for selective oligonucleotide delivery to skeletal muscle.
• Integrate human tissue datasets, transcriptomics, proteomics, single-cell and spatial biology, human genetics and experimental studies to assess receptor abundance, tissue specificity, membrane accessibility, internalisation and trafficking.
• Establish receptor-selection criteria based on expression, muscle selectivity, accessibility, internalisation kinetics, receptor recycling, cross-species conservation and potential safety liabilities.
• Assess the influence of muscle fibre type, anatomical muscle group, physiological state, age and disease context on receptor expression and delivery efficiency.
• Establish fit-for-purpose biological models to validate candidate receptors and characterise mechanisms governing productive oligonucleotide delivery.

Targeted Oligonucleotide Delivery & Proof-of-Concept

• Lead the development and biological validation of muscle-targeted AOCs and alternative delivery approaches, including peptide, lipid and small-molecule conjugates.
• Establish a quantitative experimental cascade covering receptor engagement, internalisation, cellular uptake, intracellular trafficking, productive delivery, target knockdown and functional activity.
• Develop and oversee relevant 2D and advanced 3D human skeletal muscle models, including primary muscle cells, differentiated myotubes and engineered muscle systems.
• Characterise receptor-mediated uptake, intracellular trafficking, endosomal processing and escape, and other determinants of productive oligonucleotide delivery.
• Collaborate with antibody engineering, oligonucleotide chemistry and conjugation teams to optimise targeting constructs, potency, selectivity, durability and therapeutic index.
• Define quantitative proof-of-concept criteria and stage gates based on tissue exposure, muscle-cell uptake, target engagement, magnitude and durability of knockdown, dose-response and non-target tissue selectivity.
• Lead in vivo studies to establish muscle delivery feasibility and exposure-response relationships linking dose, biodistribution, cellular uptake, target engagement and functional knockdown across relevant muscle groups.
• Establish clear go/no-go criteria for delivery robustness, reproducibility, scalability and translational potential.

Skeletal Muscle Models & In Vivo Pharmacology

• Establish an integrated preclinical capability spanning skeletal muscle cellular biology, functional pharmacology, disease modelling and in vivo pharmacology.
• Develop and apply human-relevant skeletal muscle models to assess delivery, target biology, target engagement and pharmacological response.
• Establish functional assays covering muscle differentiation, hypertrophy and atrophy, glucose uptake, insulin signalling, mitochondrial function, substrate utilisation and protein turnover.
• Select and validate in vivo models relevant to obesity, insulin resistance, metabolic dysfunction, muscle wasting and other cardiometabolic and muscle-associated diseases.
• Design and oversee single- and repeat-dose studies assessing target engagement, pharmacodynamic response, functional efficacy, durability and tolerability.
• Integrate molecular, histological, biochemical, imaging and physiological endpoints to establish robust evidence of mechanism and pharmacological efficacy.

Target Discovery & Validation

Following successful demonstration of productive muscle delivery:

• Establish a systematic strategy to identify, prioritise and validate novel skeletal muscle therapeutic targets relevant to cardiometabolic and muscle-associated diseases.
• Integrate human genetics, functional genomics, transcriptomics, proteomics, clinical datasets and disease biology to generate and prioritise therapeutic hypotheses.
• Apply ASO, siRNA and other genetic perturbation approaches to establish causal relationships between target modulation and disease-relevant muscle phenotypes.
• Leverage the established muscle-targeted delivery platform for in vivo target validation directly within skeletal muscle.
• Establish target validation cascades spanning human-relevant cellular systems, mechanistic studies and in vivo disease models.
• Investigate target effects on muscle metabolism, insulin sensitivity, mitochondrial function, substrate utilisation, muscle mass and function, protein turnover and muscle-derived endocrine signalling.
• Define go/no-go criteria incorporating human genetic evidence, biological effect size, oligonucleotide tractability, pharmacological validation, safety, translational potential and competitive differentiation.

Therapeutic Pipeline Generation

• Build a differentiated portfolio of muscle-targeted oligonucleotide programs addressing high-value opportunities in cardiometabolic and muscle-related diseases.
• Translate validated targets into ASO, siRNA and other oligonucleotide discovery programs in collaboration with NATi's discovery, chemistry and computational teams.
• Define Target Candidate Profiles (TCPs) and Preclinical Candidate Profiles (PCPs), incorporating biological rationale, patient population, required target modulation, delivery requirements, biomarkers, therapeutic index and clinical differentiation.
• Lead biology strategy from target validation through lead optimisation, in vivo proof-of-concept and Preclinical Candidate nomination.
• Integrate delivery, target engagement, functional pharmacology, biodistribution, PK/PD, translational biomarkers and safety data to guide program progression.
• Prioritise programs based on human disease relevance, target biology, delivery feasibility, therapeutic index, unmet medical need and competitive differentiation.
• Establish a sustainable discovery engine leveraging the validated muscle-targeted delivery platform across multiple therapeutic targets and programs.

DMPK, Biodistribution & Translational Strategy

• Partner with DMPK and bioanalytical teams to establish integrated PK, tissue biodistribution, cellular exposure and PK/PD strategies.
• Define quantitative exposure-response relationships linking dose, systemic exposure, tissue distribution, productive cellular uptake, target engagement and pharmacological activity.
• Evaluate oligonucleotide stability, tissue exposure, intracellular distribution and durability of pharmacological effects.
• Integrate biodistribution, target knockdown, biomarkers and functional pharmacology to guide dose selection, construct optimisation and candidate progression.
• Develop translational biomarker and pharmacodynamic strategies to bridge preclinical studies with early clinical development.
• Contribute to human dose projections, Preclinical Candidate selection and IND-enabling strategies in collaboration with relevant functional teams.

Scientific Leadership & Cross-functional Collaboration

• Establish and lead a multidisciplinary group initially focused on skeletal muscle biology, receptor identification, targeted delivery and in vivo proof-of-concept, expanding into target discovery and therapeutic pipeline development as the platform matures.
• Recruit, develop and mentor scientific talent across muscle biology, receptor biology, cellular pharmacology, target validation and in vivo pharmacology.
• Maintain direct scientific engagement in experimental strategy, study design, data interpretation and critical program decisions.
• Establish scientific platforms, SOPs and quantitative decision criteria for receptor selection, delivery validation, target validation and program progression.
• Oversee internal research activities and external CRO partnerships, ensuring scientific quality, rigour, timelines and budget alignment.
• Drive cross-functional collaboration with antibody engineering, oligonucleotide design and chemistry, conjugation, computational biology, DMPK, bioanalytics, translational sciences and clinical development.
• Contribute to Preclinical Candidate selection, IND-enabling strategies, regulatory documentation and translational development plans.
• Partner with senior management to define scientific priorities, capability requirements, portfolio strategy, resource allocation and development milestones.
• Evolve the initial delivery-enabling capability into an integrated skeletal muscle therapeutic discovery organisation.

Qualifications & Professional Attributes

• PhD in Molecular Biology, Physiology, Pharmacology, Pharmaceutical Sciences, Biochemistry or a related discipline.
• Typically, 12+ years of pharmaceutical or biotechnology R&D experience, with substantial scientific and team leadership responsibility in skeletal muscle biology, targeted therapeutics or preclinical pharmacology.
• Deep expertise in skeletal muscle biology, including fibre and cellular heterogeneity, muscle physiology, metabolism, membrane receptor biology and disease-associated changes.
• Strong understanding of cell-surface receptor biology, receptor-mediated internalisation, intracellular trafficking, endosomal processing and escape, and productive intracellular delivery mechanisms.
• Demonstrated ability to translate receptor biology and tissue physiology into therapeutic targeting strategies.
• Experience establishing and applying in vitro, ex vivo and in vivo skeletal muscle models for mechanistic biology, pharmacology and therapeutic discovery.
• Strong in vivo pharmacology experience integrating tissue exposure, target engagement, pharmacodynamic biomarkers and functional efficacy.
• Experience with targeted delivery technologies, AOCs, antibody conjugates, oligonucleotide therapeutics or other genetic medicines strongly preferred.
• Direct experience with ASO, siRNA, AOC or related targeted oligonucleotide technologies is a significant advantage.
• Experience in target discovery and validation, translating novel disease biology into drug discovery programs.
• Strong understanding of PK/PD, tissue biodistribution, exposure-response relationships, translational biomarkers and candidate selection.
• Demonstrated ability to advance complex scientific hypotheses through defined experimental milestones, proof-of-concept and quantitative go/no-go decisions.
• Proven experience establishing scientific capabilities, recruiting and developing multidisciplinary teams, and managing external CRO and research partnerships.
• Strong scientific judgement, strategic thinking and portfolio leadership, with the ability to make decisions under scientific uncertainty.
• Excellent cross-functional collaboration, communication and interpersonal skills, with the ability to inspire and lead high-performing scientific teams.