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RISS 인기검색어
- 검색키워드
- 저자 : Shopsowitz, Kevin E. (검색결과 2 건)
- 무료
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- 유료
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Roh, Young Hoon,Lee, Jong Bum,Shopsowitz, Kevin E.,Dreaden, Erik C.,Morton, Stephen W.,Poon, Zhiyong,Hong, Jinkee,Yamin, Inbar,Bonner, Daniel K.,Hammond, Paula T. American Chemical Society 2014 ACS NANO Vol.8 No.10
<P/><P>Antisense oligonucleotides can be employed as a potential approach to effectively treat cancer. However, the inherent instability and inefficient systemic delivery methods for antisense therapeutics remain major challenges to their clinical application. Here, we present a polymerized oligonucleotides (ODNs) that self-assemble during their formation through an enzymatic elongation method (rolling circle replication) to generate a composite nucleic acid/magnesium pyrophosphate sponge-like microstructure, or DNA microsponge, yielding high molecular weight nucleic acid product. In addition, this densely packed ODN microsponge structure can be further condensed to generate polyelectrolyte complexes with a favorable size for cellular uptake by displacing magnesium pyrophosphate crystals from the microsponge structure. Additional layers are applied to generate a blood-stable and multifunctional nanoparticle <I>via</I> the layer-by-layer (LbL) assembly technique. By taking advantage of DNA nanotechnology and LbL assembly, functionalized DNA nanostructures were utilized to provide extremely high numbers of repeated ODN copies for efficient antisense therapy. Moreover, we show that this formulation significantly improves nucleic acid drug/carrier stability during <I>in vivo</I> biodistribution. These polymeric ODN systems can be designed to serve as a potent means of delivering stable and large quantities of ODN therapeutics systemically for cancer treatment to tumor cells at significantly lower toxicity than traditional synthetic vectors, thus enabling a therapeutic window suitable for clinical translation.</P>
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Roh, Young Hoon,Deng, Jason Z.,Dreaden, Erik C.,Park, Jae Hyon,Yun, Dong Soo,Shopsowitz, Kevin E.,Hammond, Paula T. John Wiley and Sons Inc. 2016 Angewandte Chemie. international edition Vol.55 No.10
<P><B>Abstract</B></P><P>Packaging multiple small interfering RNA (siRNA) molecules into nanostructures at precisely defined ratios is a powerful delivery strategy for effective RNA interference (RNAi) therapy. We present a novel RNA nanotechnology based approach to produce multiple components of polymerized siRNA molecules that are simultaneously self‐assembled and densely packaged into composite sponge‐like porous microstructures (Multi‐RNAi‐MSs) by rolling circle transcription. The Multi‐RNAi‐MSs were designed to contain a combination of multiple polymeric siRNA molecules with precisely controlled stoichiometry within a singular microstructure by manipulating the types and ratios of the circular DNA templates. The Multi‐RNAi‐MSs were converted into nanosized complexes by polyelectrolyte condensation to manipulate their physicochemical properties (size, shape, and surface charge) for favorable delivery, while maintaining the multifunctional properties of the siRNAs for combined therapeutic effects. These Multi‐RNAi‐MS systems have great potential in RNAi‐mediated biomedical applications, for example, for the treatment of cancer, genetic disorders, and viral infections.</P>
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