GATA-3 is a transcription factor that is responsible for the differentiation of Th2 cells in inflammatory pathways. Due to this critical role in differentiation, targeted silencing of the GATA-3 gene has shown promise as a potential target for the treatment of inflammatory diseases. Recently a GATA-3 specific DNAzyme – a catalytically active DNA molecule – has been shown to specifically bind and cleave GATA-3 mRNA. Oftentimes highly folded nucleic acids such as DNAzymes must be chemically modified or assisted in their entry into cells by chemical transfection agents in order to maintain their chemical stability. In light of this limitation, our group has recently developed a nucleic acid nanocapsule (NAN) for delivering unmodified nucleic acid ligands with a built-in mechanism for deployment when endocytosed. We have shown that functionalization of the NAN with the GATA-3 specific DNAzyme results in a construct that is readily taken up into cells without the need for external transfection agents and which maintains its cleavage activity. Herein we show that DNAzyme NAN (DNz-NAN) can cleave truncated GATA-3 mRNA in solution, and full length GATA-3 mRNA in MCF-7 cells as quantified by qPCR, showing that the DNAzyme is able to retain its catalytic activity post attachment to the nanocapsule. Taken together the DNz-NAN has the potential to both silence a gene through mRNA cleavage while simultaneously releasing an internalized small molecule cargo. This route to co-delivery can enable the synergistic release of a therapeutic oligonucleotide and small molecule drug, with important implications in the treatment of a variety of inflammatory diseases.<br/>

Targeted gene regulation by an enzyme degradable nucleic acid nanocapsule

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.