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RNA Formulation and Delivery
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
AI-Driven High-Throughput Screening
A custom-built platform integrating machine learning with automated formulation and screening of LNP libraries, enabling rapid identification of optimal delivery systems.
Designing PEG-free LNPs
Expertise in designing biodegradable, immunologically inert amphiphilic polymers as next-generation alternatives to PEGylated lipids for improved safety and circulation profiles, and in synthesizing biodegradable ionizable lipids.jpg?sfvrsn=40e82934_0 "Designing PEG free LNPs (resized)")
Targeted siRNA Conjugation Technologies
Development of modular conjugation strategies to link siRNA with cell-specific ligands, achieving precise and effective gene silencing.
Extrahepatic RNA Delivery Platforms
Proprietary LNP formulations engineered for efficient and selective RNA delivery to extrahepatic tissues, including lymph nodes, skin, and immune cells.
Our Technologies
PEG-Free LNP Platform
Innovative amphiphilic polymers that are biodegradable and immunologically inert, developed as safe and effective replacements for PEG in lipid nanoparticles.Ionizable Lipid Design & Engineering
Ionizable lipid technologies optimized for formulation performance across diverse RNA delivery applications.Extrahepatic RNA Delivery Systems
Delivery systems that modulate biodistribution and cellular uptake to achieve targeted RNA delivery outside the liver. This enables precise RNA therapeutics for immune-related and tissue-specific applications.
The Team
.jpg?sfvrsn=ce101720_0 "Yang Yi Yan (resized)")
Professor Yang Yi Yan
Distinguished Principal Scientist
Division Director and Group Leader
.jpg?sfvrsn=2a6190f7_0 "Yang Chuan (resized)")
.jpg?sfvrsn=35a949fe_0 "Zhao Xinxin (resized)")
.jpg?sfvrsn=b4a03800_0 "Xiong Qiancheng (resized)")
.jpg?sfvrsn=5e68d777_0 "Zeng Jinyue (resized)")
.jpg?sfvrsn=7bf2e986_0 "Joyce Tay (resized)")
.jpg?sfvrsn=3e382bfd_0 "Liu Xinyan (resized)")
.jpg?sfvrsn=403142ee_0 "Zhang Li (resized)")
.jpg?sfvrsn=288fb979_0 "Zhang Yue (resized)")
.jpg?sfvrsn=12627af6_0 "Zhao Gui (resized)")
.jpg?sfvrsn=c4e9eec6_0 "Zhu Chenxian (resized)")
Our Track Record
Featured Publications
- Dao Thi Hong Le, Chuan Yang, Yue Zhang, Gui Zhao, Melgious J Y Ang, Ki Hyun Bae, James H P Hui, James L Hedrick and Yi Yan Yang (2025) Replacing PEG-Lipid with Amphiphilic Polycarbonates in mRNA-Loaded Lipid Nanoparticles: Impact of Polycarbonate Structure on Physicochemical and Transfection Properties. Biomacromolecules 26(6): 3563-3575
- Jin-Yue Zeng, Shonya Lingesh, Nithiyaa D/O Bala Krishnan, Brandon Seow Yi Loong, Min Liu, Qingfeng Chen and Yi Yan Yang (2025) Cholesterol-Derived Mannosylated Polypeptide-Formed Lipid Nanoparticles for Efficient in Vivo mRNA Delivery. Small Methods 9(6): e2401712
- Nipuni Maniyamgama, Ki Hyun Bae, Zi Wei Chang, Jialing Lee, Melgious J. Y. Ang, Yong Jie Tan, Lisa F. P. Ng, Laurent Renia, Kevin P. White and Yi Yan Yang (2025) Muco-Penetrating Lipid Nanoparticles Having a Liquid Core for Enhanced Intranasal mRNA Delivery. Advanced Science 12(11): e2407383
- Li Zhang, Brandon Yi Loong Seow, Ki Hyun Bae, Yue Zhang, Kuo-Chieh Liao, Yue Wan and Yi Yan Yang (2025) Role of PEGylated lipid in lipid nanoparticle formulation for in vitro and in vivo delivery of mRNA vaccines. Journal of Controlled Release 380: 108-124
- Kuo-Chieh Liao, Majid Eshaghi, Zebin Hong, Tzuen Yih Saw, Jian An Jovi Lim, Jian Han Han, Jong Ghut Ashley Aw, Kiat Yee Tan, Aixin Yap, Xiang Gao, Youzhi Anthony Cheng, Su Ying Lim, You Zhi Nicholas Cheang, Wilfried A A Saron, Abhay P S Rathore, Li Zhang, Bhuvaneshwari Shunmuganathan, Rashi Gupta, Siang Ling Isabelle Tan, Xinlei Qian, Kiren Purushotorman, Nagavidya Subramaniam, Leah A Vardy, Paul A Macary, Ashley John, Sylvie Alonso, Yi Yan Yang, Haiwei Song, Roland G Huber and Yue Wan (2025) Characterization of group I introns in generating circular RNAs as vaccines. Nucleic Acids Research 53: gkaf089
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