Poster abstracts

Poster number 14 submitted by Maricarmen Gonzalez

GalNAc Nanoparticles using Melamine and Cyanuric Acid for Nucleic Acid Delivery

Maricarmen Gonzalez (Department of Chemistry and Biochemistry)

Abstract:
Modification of drug delivery methods in order to provide a specific target prevents damaging healthy cells while potentially increasing or retaining efficacy. N-acetyl galactosamine (GalNAc) is a selective compound that binds to the asialoglycoprotein receptor (ASPGR) found on hepatocytes. Utilizing this selectivity, several non-covalent GalNAc delivery methods that encapsulate nucleic acids were developed by our group. One method involves the self-assembly of melamine cationic lipids and cyanuric acid GalNAc conjugates that form capsule-like nanoparticles with nucleic acids as cargo. The other approach utilizes a molecular organic framework (MOF) using H-M, 2-MIM, and Zn(NO3)2 which forms zeolitic imidazolate frameworks (Zif-8s) that encapsulate nucleic acids. Our aim is to increase the selectivity of nucleic acid delivery to hepatocytes without directly modifying DNA/RNA. Additionally, we have designed a new bPNA, Acetyl-K2B-Ala-K2B, which will further our DNA/RNA molecular recognition studies.

References:
1. Nair, J. K.; Willoughby, J. L. S.; Chan, A.; Charisse, K.; Alam, M. R.; Wang, Q.; Hoekstra, M.; Kandasamy, P.; Kel’in, A. V.; Milstein, S.; Taneja, N.; O’Shea, J.; Shaikh, S.; Zhang, L.; van der Sluis, R. J.; Jung, M. E.; Akinc, A.; Hutabarat, R.; Kuchimanchi, S.; Fitzgerald, K.; Zimmermann, T.; van Berkel, T. J. C.; Maier, M. A.; Rajeev, K. G.; Manoharan, M. Multivalent N-Acetylgalactosamine-Conjugated siRNA Localizes in Hepatocytes and Elicits Robust RNAi-Mediated Gene Silencing. J. Am. Chem. Soc. 2014, 136 (49), 16958–16961.
2. Poddar, A.; Conesa, J. J.; Liang, K.; Dhakal, S.; Reineck, P.; Bryant, G.; Pereiro, E.; Ricco, R.; Amenitsch, H.; Doonan, C.; Mulet, X.; Doherty, C. M.; Falcaro, P.; Shukla, R. Encapsulation, Visualization and Expression of Genes with Biomimetically Mineralized Zeolitic Imidazolate Framework-8 (ZIF-8). Small 2019, 15 (36), e1902268.

Keywords: Drug Delivery, GalNAc, Nanoparticles