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Engineering Next-Generation RNA Therapeutics
The RNA Formulation and Delivery Group develops safe and effective nanocarriers for targeted RNA therapeutics. We engineer next-generation lipid nanoparticles (LNPs) and siRNA-ligand conjugates to overcome major limitations of current systems—such as liver accumulation, accelerated blood clearance (ABC) effect, poor extrahepatic targeting, and limited endosomal escape. Our goal is to advance RNA delivery platforms that enable greater precision, efficacy, and translational impact in RNA-based therapies.
Focus Areas
- AI-Assisted LNP Design: Leveraging machine learning to develop novel lipids and LNPs for specific organ and cell targeting, with minimal immunogenicity.
- PEG-Free Nanocarriers: Designing biodegradable, immunologically inert alternatives to PEG, and biodegradable ionizable lipids for enhanced delivery and repeat dosing.
- Immune Cell-Targeted Delivery: Engineering LNPs for selective mRNA delivery to T cells and macrophages to advance in vivo immunotherapies.
- Skin-Targeted mRNA Therapeutics: Developing LNPs for treating skin diseases through keratinocyte-directed mRNA delivery.
- siRNA-Ligand Conjugates: Creating ligand-guided siRNA constructs to achieve cell-specific gene silencing with improved safety and efficacy.
Our Capabilities
Stem Cell Expansion
We develop scalable stem cell expansion platforms using microcarrier and aggregate suspension cultures in bioreactors, enabling consistent production of high-quality pluripotent and mesenchymal stem cells.Stem Cell Differentiation
We establish robust, scalable workflows to differentiate stem cells into functional cell types, supporting research, therapeutic development, and cell and gene therapy manufacturing.Media Formulation
We develop chemically defined, xeno-free, serum-free media optimized for stem cell expansion and differentiation, enhancing performance and reproducibility across bioprocess platforms.
Our Technologies
Aggregate-Based Suspension System
- Robust and scalable: Supports high-density hiPSC aggregate cultures with 15-25-fold expansion, suitable for allogeneic iPSCs manufacturing
- High-Yield Differentiation: Drives robust, reproducible hiPSC-to-immune differentiation, delivering 10⁴-fold expansion at industrial scale
Microcarrier-based Bioreactor System
- Robust and scalable: Proven across pluripotent and mesenchymal stem cells, delivering 3-10-fold higher yields compared with conventional 2D cultures
- Reprogramming on MCs: Enables >30-fold enhancement in reprogramming efficiency, outperforming standard monolayer approaches
- Validated for hiPSC expansion and differentiation into red blood cells (RBCs) and cardiomyocytes, delivering high yield and high quality
The Team
Our Track Record
Featured Publications
- Tom A Wyrobnik, Laia Miranda, Alan Lam, Steve Oh, Andrea Ducci and Martina Micheletti (2025) Scalable, High-Density Expansion of Human Mesenchymal Stem Cells on Microcarriers Using the Bach Impeller in Stirred-Tank Reactors. Biotechnology and Bioengineering 122(10): 2803-2818
- Alan Tin Lun Lam, Premkumar Jayaraman, Abigail Becker, Ryan Lim, Kim Leng Teo, Jacqueline Ng and Steve Oh (2023) Human Mesenchymal Stem Cell Processing for Clinical Applications Using a Closed Semi-Automated Workflow. Journal of Visualized Experiments 193
- Alan Tin Lun Lam, Valerie Ho, Svetlan Vassilev, Shaul Reuveny and Steve Kah Weng Oh (2022) An allied reprogramming, selection, expansion and differentiation platform for creating hiPSC on microcarriers. Cell Proliferation 55:e13256
- Alan Tin-Lun Lam, Alison P. Lee, Premkumar Jayaraman, Kah Yong Tan, Deepak Raghothaman, Hsueh Lee Lim, He Cheng, Lihan Zhou, Andy Hee-Meng Tan, Shaul Reuveny and Steve Oh (2021) Multiomics analyses of cytokines, gene, miRNA, and pathway regulatory networks in human mesenchymal stem cells expanded in stirred microcarrier-spinner cultures. Stem Cell Research 53:102272
- Jaichandran Sivalingam, Yu SuE, Zhong Ri Lim, Alan T.L. Lam, Alison P. Lee, Hsueh Lee Lim, Hong Yu Chen, Hong Kee Tan, Tushar Warrier, Jing Wen Hang, Nazmi B. Nazir, Andy H.M. Tan, Laurent Renia, Yuin Han Loh, Shaul Reuveny, Benoit Malleret and Steve K.W. Oh (2020) A Scalable Suspension Platform for Generating High-Density Cultures of Universal Red Blood Cells from Human Induced Pluripotent Stem Cells. Stem Cell Reports 16(1): 182-197
- Alan Tin-Lun Lam, Allen Kuan-Liang Chen, Sherwin Qi-Peng Ting, Shaul Reuveny and Steve Kah-Weng Oh (2016) Integrated processes for expansion and differentiation of human pluripotent stem cells in suspended microcarriers cultures. Biochemical and Biophysical Research Communications 473(3): 764-8
Landmark Patent & IP
- Microcarriers for stem cell culture (2014)
- Culture of pluripotent and multipotent cells on microcarriers (2014)