Develop safe and efficient nucleic acid delivery systems
Advance the clinical translation of RNA therapeutics
Research Areas:
(1) AI-enabled rational design of lipid molecules and mRNA sequence elements, investigation of the in vivo delivery mechanisms of lipid nanoparticle systems, and development of safe, efficient, and precise RNA delivery platforms;
(2) Development of novel inhalable RNA delivery systems to overcome challenges in lung-targeted delivery, establishing a versatile technological platform for pulmonary nucleic acid therapeutics, with applications in respiratory diseases such as pulmonary fibrosis, asthma, and lung cancer;
(3) Engineering next-generation programmable and injectable hydrogel-based multifunctional implantable biomaterials to achieve spatiotemporally controlled delivery of drugs or cytokines in vivo, thereby expanding their applications in regenerative medicine.
Rational Design of Lipids
A combinatorial chemistry strategy is employed to enable the modular design of ionizable amines, hydrophobic lipid tails, and linker chemistries. By integrating artificial intelligence (AI) with innovative synthetic methodologies, multifunctional lipid libraries are constructed. Lipid nanoparticles (LNPs) with high RNA encapsulation efficiency are subsequently formulated. Through systematic structural optimization, the interactions between LNPs and biological systems are precisely regulated, enabling the efficient development and screening of RNA carrier libraries, including highly safe and effective LNPs as well as low liver-accumulating LNP variants.
Representative Publications: Journal of the American Chemical Society, 2025; ACS Nano, 2024; ACS Nano, 2022
Inhalable Lung-Targeted RNA Delivery Systems
An innovative inhalable RNA delivery platform has been developed to advance therapeutic strategies for respiratory diseases. To address key challenges associated with aerosolized LNPs, including particle size enlargement, reduced encapsulation efficiency, and limited mucus penetration, this approach integrates multidimensional optimization of lipid structures, formulation design, and manufacturing processes. The resulting system exhibits excellent aerosolization stability, favorable aerodynamic properties, and efficient mucus penetrating capability. It has demonstrated robust gene regulation and significant therapeutic efficacy across multiple models of respiratory diseases.
Representative Publications: Nature Communications, 2025; Nature Communications, 2025; Nature Communications, 2024 (ESI Highly Cited Paper); Science Advances, 2022 (ESI Highly Cited Paper)
Targeted Lipid Delivery Systems
A modular lipid co assembly strategy has been developed to enable targeted nucleic acid delivery and drive innovation in therapeutic mechanisms for major diseases. This approach introduces a “modular molecular assembly” concept, in which functional lipid modules with targeting capabilities are rationally designed and assembled to construct nucleic acid carriers capable of efficient and selective delivery to specific cell types, including hepatic stellate cells, macrophages, and microglia. A “positive feedback enhanced” targeting mechanism is proposed for the first time, enabling amplified delivery efficiency and therapeutic outcomes. This platform has demonstrated significant efficacy in animal models of cardiovascular, cerebrovascular, and hepatic metabolic diseases, providing new avenues for the treatment of major diseases.
Representative Publications: Nature Communications, 2023; ACS Nano, 2024; ACS Nano, 2024; ACS Nano, 2023; ACS Nano, 2023