Antisense Oligonucleotides and Splicing
PhD – National University of Singapore
PhD – National University of Singapore
Email: ttabaglio@a-star.edu.sg
SUMMARY
Dr. Tommaso Tabaglio is a biotech entrepreneur and a Group Leader at A*STAR's Institute of Molecular and Cell Biology (IMCB). His career is distinguished by a dynamic blend of academic research and industry experience. He co-founded two startups, ImmuNOA Pte. Ltd. and TechNOA, focusing on antisense oligonucleotide applications. As Chief Scientific Officer, he successfully guided ImmuNOA's scientific vision in cancer immunotherapy until 2024. His industry experience also includes developing diagnostic pipelines at AMT Advanced MedTech during the COVID-19 pandemic. Dr. Tabaglio's work has resulted in publications detailing a platform nanotechnology for RNA delivery, a novel system for unveiling SSO chemical modification patterns, a new therapeutic approach for a urea cycle disorder, and a rapid test for SARS-CoV-2 cellular immunity.
KEY AWARDS & GRANTS
- 2026: NIRBA Cluster 4
- 2026: WuXi Solitaire Grant
- 2024: STDR – Selective targeting isoform-specific FynT tyrosine kinase
- 2014: SINGA Scholarship award
RESEARCH
Dr. Tabaglio's research is focused on pioneering RNA therapeutics, from fundamental mechanistic studies to translational therapies. His work centres on developing and testing new oligo chemistries and delivery mechanisms for nucleic acid therapeutics, working at the edge of biology and chemistry. A key contribution is the creation of the NATURA Platform, a novel, high-throughput reporter system designed for the optimization of splice-switching oligonucleotide (SSO) chemistry. This innovative, sequence-agnostic platform, which detects the functional uptake of various RNA-targeting molecules, has been adopted by multiple international laboratories. As a Group Leader, he leads significant research initiatives in both chronic and genetic diseases. His work is characterized by a strong focus on commercially viable science, as evidenced by four key patents in RNA therapeutics.
PUBLICATIONS
- A synergistic interaction between PRMT5 and LSD1 inhibitors in AML.
NJ Param, E Arceci, F Fiorentino, L Pignata, D Torre…（2026）
Science Advances.
- BLOC1S1 depletion via splice-switching oligonucleotides improves mitochondrial respiration and rescues ALS phenotypes.
JH Hor, JR Ow, W Ng, B Ramasamy, T Tabaglio…（2026）
Molecular Therapy. - Developing splice-switching oligonucleotides for urea cycle disorder using an integrated diagnostic and therapeutic platform.
JR Ow, E Imagawa, F Chen, WY Cher, SYT Chan…（2025）
Journal of Hepatology.
- Nature-inspired platform nanotechnology for RNA delivery to myeloid cells and their bone marrow progenitors.
SRJ Hofstraat, T Anbergen, R Zwolsman, J Deckers…（2025）
Nature Nanotechnology. - Unveiling sequence-agnostic mixed-chemical modification patterns for splice-switching oligonucleotides using the NATURA platform.
T Tabaglio, T Agarwal, WY Cher, JR Ow, AK Chew…（2025）
Molecular Therapy Nucleic Acids.
- Hepatocyte-intrinsic SMN deficiency drives metabolic dysfunction and liver steatosis in spinal muscular atrophy.
DMK Leow, YK Ng, LC Wang, HWL Koh, T Zhao…（2024）
The Journal of clinical investigation.
PATENTS
- Splice-switching Oligonucleotide (SSO) Targeting OTC-PE5 as Therapeutics Candidates for Ornithine Transcarbamylase (OTC) Deficiency Disorders (WO2025151083A1)
The invention concerns splice-switching oligonucleotides that alter the splicing of a variant OTC pre-mRNA. By excluding the OTC-PE5 pseudoexon, the oligonucleotides are intended as therapeutic candidates for urea-cycle disorders, particularly ornithine transcarbamylase deficiency. - SSOs capable of altering the splicing of a pre-mRNA encoding a variant of the SLC25A13 gene (WO2024005715A1)
The invention concerns splice-switching oligonucleotides that alter the splicing of a variant OTC pre-mRNA. By excluding the OTC-PE5 pseudoexon, the oligonucleotides are intended as therapeutic candidates for urea-cycle disorders, particularly ornithine transcarbamylase deficiency. - DNA Construct and Nucleic Acid Compound Tools (WO2025071493A1)
The invention provides a DNA construct with frame-switch and reporter exons whose alternative splicing changes which reporter gene is in frame. The system is designed to characterize functional cellular uptake and delivery efficacy of nucleic-acid therapeutics. - Method of identifying a chemical modification pattern (WO2025151083A1/10202403247X)
The invention identifies chemical-modification patterns that improve the splice-modulation efficiency of single-stranded RNA oligonucleotides. It compares defined combinations of 2'-ribose modifications and constrained nucleotides, then measures splicing performance to select higher-efficiency patterns.