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Cell-specific and multifunctional drug delivery in vivo has been regarded as one of the most challenging issues in the field of drug delivery. A wide variety of cell types in humans still cannot be efficiently and specifically reached by delivery systems such as lung epithelial cells, metastatic tumor cells, and tumor stem cells. An even more formidable task is delivering multiple payloads into specific cells and tissues. In order to address these challenges, my laboratory will work in the following areas: 1) to develop cell specific drug delivery systems; 2) to construct multifunctional drug delivery systems; 3) to demonstrate therapeutic efficacy of these systems in animal models for treating genetic disorders, infectious diseases, as well as cancers.

 

1. Messenger RNA (mRNA) based therapeutics have shown great promise for expressing functional antibodies and proteins. Clinical studies have explored mRNA for use as vaccines through local administration of naked mRNA or mRNA-transfected dendritic cells in order to induce antigen-specific immune responses. Recently, extensive efforts have been devoted to achieving the systemic delivery of mRNA using liposomes, polymeric nanoparticles, and mRNA-protein complexes. Although significant advances have been made, development of new mRNA carriers remains a fast-growing field in order to improve delivery efficiency and maximize the therapeutic window of mRNA therapeutics in humans.

Li, B.; Luo, X.; Deng, B.; Wang, J.; McComb, D. W.; Shi, Y.;  Gaensler, K. M. L.; Tan, X.; Dunn, A. L.; Kerlin, B. A.; Dong, Y.* An Orthogonal Array Optimization of Lipid-like Nanoparticles for mRNA Delivery in Vivo, Nano Letters, 15(12):8099-8107 (2015). PMID: 26529392

 

2. Chemically modified nucleotides play significant roles in the effectiveness of mRNA translation. Numerous strategies for mRNA modification have been investigated to improve translation efficiency and reduce immunogenicity, including modifications at the 5’ cap, 5’ and 3’-untranslated regions, the coding region, and the poly(A) tail. Incorporation of chemically modified nucleotides into mRNAs is one of the effective approaches reported in the literature.

 

Li, B., Luo, X., Dong, Y.* Effects of Chemically Modified Messenger RNA on Protein Expression, Bioconjugate Chemistry, doi: 10.1021/acs.bioconjchem.6b00090