Research

Synthesizing Biodegradable Ionizable Lipids for Targeted Nucleic Acid Delivery

Our group is the first to include a disulfide bond to construct a combinatorial library of ionizable lipids. These materials are biodegradable and stimulus-responsive delivery nano vectors, capable of delivering and releasing their cargo in response to the physiological environment. These novel bioreducible lipids show high delivery efficiency of various nucleic acid-based cargos and low cytotoxicity compared with other commercially available lipid-based carriers. Because this combinatorially synthesized lipid library comprises many molecules with slight structural variations, we have been able to correlate molecular features to the transport efficiency of biological cargo. We also found that these Lipid Nanoparticles (LNPs) can deliver cargo in an organ-specific manner. We have delivered specific mRNA through intravenous injection into the liver, lung, kidney, and spleen. Furthermore, we successfully demonstrated that these materials can carry various cargo that cross the blood-brain barrier. 

Featured Publications

Engineering Lipid Nanoparticle-Based Systems for Vaccine and Cancer Immunotherapy

Our group has been applying Lipid Nanoparticles (LNPs) for vaccine development and cancer immunotherapy. We have developed several strategies. We demonstrated an lipid nanoparticle system with lymph node targeting ability for delivery of mRNA-based vaccines for cancer and infectious diseases. The second strategy is to enhance the tumor antigen capture and cross-presentation. We developed an in situ vaccination approach using lipid nanoparticles to achieve simultaneously enhancing cross-presentation and STING activation and demonstrated the inhibition of the tumor growth in the B16F10 allograft model tumor model with excellent immune memory.

Featured Publications

Developing a Non-Viral Approach for Gene Editing

Our group has been developing new synthetic lipid-based nanoparticles to deliver both Cas9 protein and mRNA for genome editing. Genome-editing technologies hold tremendous potential for treating genetic diseases. We are exploring a nonviral approach using synthetic Lipid Nanoparticles (LNPs) to solve the delivery challenge for gene editing. In one example, we showed a fast and very potent CRISPR/Cas9 genome editing in vitro and in vivo, enabled by simultaneous delivery of Cas9 mRNA and sgRNA using our bioreducible lipid nanoparticles. We also demonstrated the efficient delivery of PCSK9 and Angptl3 genes to control the cholesterol level in mice, which can potentially lead to clinical translation.

Featured Publications

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