About NATiThe 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 RNA scientists with deep translational expertise to join us in advancing the next generation of RNA-based therapeutics.
Position OverviewWe 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 Accountablities
Own end-to-end scientific strategy from target validation through hit-to-lead and lead optimisation
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 rigour, reproducibility, and transparency across discovery activities
Core Scientific ResponsibilitiesOligonucleotide Discovery & Screening
Design, execute, and optimise 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, prioritisation, 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 optimisation and selection
Select and justify disease-relevant in vivo models for:
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, remodelling, and endocrine signalling
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
