A Multi-RNAi Microsponge Platform for Simultaneous Controlled Delivery of Multiple Small Interfering RNAs

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...

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Bibliographic Details
Published in:Angewandte Chemie 2016-03, Vol.128 (10), p.3408-3412
Main Authors: Roh, Young Hoon, Deng, Jason Z., Dreaden, Erik C., Park, Jae Hyon, Yun, Dong Soo, Shopsowitz, Kevin E., Hammond, Paula T.
Format: Article
Language:English
Subjects:
Biomedical materials
Cancer
Chemistry
Circular DNA
Circularity
Condensation
Deoxyribonucleic acid
Disorders
DNA
DNA/RNA-Nanotechnologie
Gene expression
Genes
Genetic disorders
Interference
Krebs
Microstructure
Nanostructure
Nanotechnology
Packaging
Physicochemical properties
Polyelectrolytes
Polymerization
Ribonucleic acid
Ribonucleic acids
RNA
RNA-Interferenz
RNA-mediated interference
siRNA
siRNA-Transport
Stoichiometry
Surface charge
Therapy
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Summary: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. Mehrere kleine interferierende RNA(siRNA)‐Moleküle wurden durch Rolling‐circle‐Transkription assembliert und zu schwammartigen porösen Komposit‐Mikrostrukturen (Multi‐RNAi‐MS) verpackt. Innerhalb jeder einzelnen Mikrostruktur wurde die Stöchiometrie der unterschiedlichen polymeren siRNA‐Moleküle durch Auswählen der Arten und Verhältnisse der ringförmigen DNA‐Template genau kontrolliert.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.201508978