Day 2Thursday, October 16, 2025 - UTC+08:00

The Nucleic Acid Therapeutics Initiative (NATi) is Singapore’s national platform to accelerate RNA drug and vaccine development through a robust translational engine. In this keynote, Dr Mohamed ElSayed will share how NATi is transforming Singapore into a globally competitive hub for RNA innovation. By integrating public research, biotech agility, and strategic partnerships, NATi bridges the translational gap enabling rapid progression from discovery to early clinical development. The initiative focuses on high-value clinical assets, modular technology platforms, targeting unmet needs in immunology, ophthalmology, and cardiometabolic diseases. NATi also plays a critical role in pandemic preparedness, leveraging RNA’s speed and scalability. This presentation will highlight how NATi catalyzes biotech formation, enriches local talent, and drives commercial value—positioning Singapore at the forefront of RNA medicine.

• Overview of mRNA and its traditional role in vaccine
• Overview of mRNA applications beyond vaccines
• 2-3 examples of alternative mRNA use
• Current challenges in the application of mRNA beyond vaccines

• Synthetic, enzymatically produced DNA is shaping the future of mRNA manufacture: rapid, scalable GMP-grade production capable of handling complex sequences and long poly A tails without the bacterial contaminants.
• Explore opDNA®, an application-specific IVT template open at the 3’ end, facilitating direct use in the IVT reaction without enzymatic linearization. As a linear template without bacterial backbone sequences, equivalent mRNA yields are achieved with less DNA mass.
• Homologous recombination of polyA tails in bacterial hosts is a major limitation of plasmid DNA. 4basebio’s enzymatic platform can handle long polyA tails (>180 bp) encoded directly into the template, while our novel polyA analytics ensure homogeneity in every construct.
• Clinically validated and regulatory-ready, opDNA® supports efficient, flexible, and compliant manufacturing. This approach can support clinical programs at every scale, from large-scale production to small-batch and scale-out demands of personalized immunotherapies.

• Identification of conserved structural motifs in viral RNA using computational and experimental approaches, revealing functional elements applicable to synthetic mRNA design for enhanced stability and translation
• Analysis of structure-function relationships in viral RNA regions and their application in optimizing mRNA therapeutics for improved cellular uptake, reduced immunogenicity, and controlled protein expression

• Insights and innovations in the scale-up of oligonucleotide synthesis
• Holistic approach to CMC challenges to advance pipelines to Clinic

• Duchenne muscular dystrophy (DMD) is most commonly caused by genomic deletions in the dystrophin gene that disrupt the reading frame and prevent synthesis of the functional 427 kDa protein. The dystrophin gene is one of the largest found in the human genome, with 79 exons spanning 2,300 kb that is processed into a 14 kb mRNA. Individuals with the milder allelic form of Becker muscular dystrophy (caused by in-frame genomic deletions) provide unequivocal proof that many dystrophin exons are not essential for normal function. Hence targeted exon skipping uses antisense oligomers to allow a DMD dystrophin pre-mRNA to be processed into the type of mRNA found in Becker MD patients.
• The first demonstration of specific exon skipping to by-pass a nonsense mutation in a mouse model of DMD in vitro was published 1999. After experiments to refine the approach in human cultured myogenic cells, results from the first human clinical trial were published less than a decade later showing localized restoration of dystrophin expression after a single blind, placebo-controlled dose escalation proof of concept study. Subsequent (and on-going) trials involving systemic delivery eventually resulted in accelerated FDA approval of three different morpholino oligomers targeting different dystrophin exons.
• Where from here? While it took many years for clinical approval of these DMD-specific drugs, groundwork was established, as was proof that antisense oligomers could change disease progression. Many other applications are now being evaluated, with the current benchmark set in Boston: diagnosis of a mutation causing Batten’s disease, design and evaluation of an exon skipping drug in patient cells and FDA approval for treatment in 10 months… for a single patient! Abnormal pre-mRNA splicing has been recognised as a common cause of disease and there is intense interest in personalised medicines for many different diseases caused by mutations amenable to splice switching antisense oligomers.
• Finally, alternative splicing allows multiple transcripts to be generated from a single gene. In some cases, different spliceoforms from the same gene have diametrically opposed functions. The use of splice switching antisense oligomers to redirect expression of a disease-associated isoform into a protective transcript should have enormous potential in many conditions, including inflammation, COVID infection and even ageing.

• Unlocking strategic investment opportunities by connecting global pharma and venture capital with emerging RNA innovators and startups across APAC.
• Driving collaborative pipelines between international pharma and APAC biotech through co-development deals, technology sharing, and regional commercialization strategies.
• Showcasing Asia-Pacific as a hub for external innovation, with growing biotech ecosystems, supportive policy environments, and robust clinical trial and manufacturing capabilities.