Scientist / Senior Scientist (RNA Drug Discovery), Cardiovascular & Metabolic Diseases Full-time

Scientist / Senior Scientist (RNA Drug Discovery), Cardiovascular & Metabolic Diseases

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.

We are seeking a Scientist / Senior Scientist (RNA Drug Discovery), Cardiovascular & Metabolic Diseases to provide scientific ownership and leadership of early discovery oligonucleotide (siRNA / ASO) programs across MASH, obesity, and cardiometabolic diseases. This role is responsible for hit identification through lead generation, integrating in-vitro screening, in-vivo pharmacology, and translational strategy with a strong emphasis on liver biology, while incorporating adipose and skeletal muscle contributions to obesity and metabolic dysfunction. The successful candidate will combine deep hands-on experimental expertise with program-level leadership, mentoring junior scientists and partnering closely with senior management to deliver company strategy.

Primary Responsibilities:

• Own end-to-end scientific strategy from target validation through hit-to-lead and lead optimization
• Serve as scientific lead for one or more oligonucleotide discovery programs in MASH and obesity
• Design and govern integrated in vitro to in vivo screening cascades supporting translational decision making
• Drive clear, defensible go/no-go decisions based on integrated biology, PK/PD, and disease-relevant endpoints
• Ensure scientific rigor, reproducibility, and transparency across discovery activities

Core Scientific Responsibilities:

• Design, execute, and optimize in vitro screening cascades for siRNA/ASO programs, including:
• Knockdown potency and dose-response assays
• Mechanistic and functional cell-based assays
• Target engagement and pathway modulation
• Lead hit identification, prioritization, and lead generation for metabolic and obesity programs
• Ensure alignment of in vitro potency, functional biology, and translational relevance

Pharmacology & Translation:

• Design and interpret in vivo PK/PD, tissue distribution, and knockdown efficacy studies
• Establish exposure-response relationships to guide lead optimization and selection
• Select and justify disease-relevant in vivo models for:
• MASH
• Obesity and insulin resistance
• Metabolic dysfunction associated with obesity
• Interpret liver histopathology and disease scoring, including:
• Steatosis, inflammation, ballooning, and fibrosis
• Alignment of preclinical endpoints with human MASH and obesity clinical readouts

Disease Biology Expertise:

• Deep expertise in liver biology with strong understanding of:
• MASH pathophysiology
• Hepatic lipid handling, inflammation, and fibrosis
• Translational biomarkers for MASH and obesity-related liver disease
• Obesity biology, including:
• Energy balance and metabolic regulation
• Adipose tissue inflammation, remodeling, and endocrine signaling
• Skeletal muscle metabolism, insulin sensitivity, and glucose utilization
• Systems-level understanding of liver-adipose-muscle crosstalk in obesity-driven MASH

Scientific Governance, Leadership & Collaboration:

• Author, implement, and maintain SOPs for in vitro screening, in vivo PK/PD and efficacy models, tissue distribution, and early tolerability workflows
• Lead or support IACUC / local animal ethics submissions, umbrella protocols, and ensure full regulatory and ethical compliance
• Mentor, train, and technically guide junior scientists and research staff, fostering high scientific standards and accountability
• Serve as the primary biology/pharmacology interface with chemistry, bioinformatics, pathology, analytical teams, CROs, and external partners
• Partner closely with senior management to align scientific execution with company strategy, portfolio priorities, and timelines

Qualifications & Experience:

• PhD in Molecular Biology, Pharmacology, Biochemistry, Toxicology, or related discipline with proven leadership of oligonucleotide (siRNA / ASO) discovery programs
• At least 5 years of relevant work experience
• Strong hands-on expertise in cell-based screening, mechanistic assays, in vivo PK/PD and knockdown biology, and execution and interpretation of obesity and MASH models
• Demonstrated success in early drug discovery, from target validation through hit identification and lead generation
• Scientifically rigorous, data-driven decision maker with excellent communication skills and ability to engage senior and cross-functional stakeholders
• Collaborative team leader and mentor, able to balance hands-on experimentation with strategic program ownership and alignment to company goals