Poster abstracts
Poster number 14 submitted by Maricarmen Gonzalez
Self-Assembly of GalNAc-Cyanuric Acid and Melamine Derivatives as a Nucleic Acid Delivery System
Maricarmen Gonzalez (Department of Chemistry and Biochemistry), Dr. Shekaraiah Devari (Department of Chemistry and Biochemistry), Dr. Dennis Bong (Department of Chemistry and Biochemistry)
Abstract:
We have designed and synthesized GalNAc-coated nanoparticles that carry DNA plasmid cargo for hepatocyte-targeted delivery and directed protein expression. Nanoparticle assembly is driven by cyanuric acid (CA) and melamine (M) recognition. Hydrocarbon chains terminated with tertiary amino groups at one end and melamine at the other were synthesized to yield carbon chains of 4-8 in length. Similarly, hydrocarbon chains of C4-C8 in length were synthesized with N-Acetylgalactosamine (GalNAc) at one end and cyanuric acid at the other. GalNAc is bound by the asialoglycoprotein receptor found on the surface of liver cells and is well-established as a ligand for liver-targeted delivery. A bromide-terminated GalNAc chain was used to alkylate a dibenzylated cyanuric acid derivative that enables monoalkylation. The cationic melamine lipids electrostatically coat the DNA backbone to form a loose particle assembly (~800 nm), which is condensed by treatment with the CA-GalNAc lipid, resulting in ~200 nm particles with low polydispersity. Consequently, the self-assembly results in a nucleic acid enclosed GalNAc complex in the form of DNA-M-CA-GalNAc, which may then be able to enter cells through receptor mediated endocytosis. Current studies are focused on the evaluation of plasmid delivery as judged by expression of RFP, as well as optimization of delivery as a function of hydrocarbon chain length.
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