Systemic Delivery of siRNA by Chimeric Capsid Protein: Tumor Targeting and RNAi Activity in Vivo

Title
Systemic Delivery of siRNA by Chimeric Capsid Protein: Tumor Targeting and RNAi Activity in Vivo
Authors
최경미김광명권익찬김인산안형준
Keywords
siRNA; Drug delivery; systemic delivery; capsid protein; tumor targeting; recombinant protein
Issue Date
2013-01
Publisher
Molecular pharmaceutics
Citation
VOL 10, NO 1, 18-25
Abstract
Recently, we reported that a chimeric capsid protein assembled into a macromolecular container-like structure with capsid shell and the resulting siRNA/capsid nanocarrier complexes efficiently suppressed RFP gene expression in the cell culture system. To extend RNAi to the in vivo applications, we here demonstrated that the siRNA/ capsid nanocarrier complexes could have tumor-specific targeting ability in vivo as well as the increased stability of siRNA during body circulation. When systemically administered, our siRNA/capsid nanocarrier complexes delivered siRNA to tumor tissues and efficiently suppressed RFP gene expression in tumor-bearing mice. The enhanced longevity of siRNA in vivo could be explained by shielding effect derived from the capsid shell, where the encapsulated siRNAs are protected from nucleases in plasma. The multivalent RGD peptides on shell surface, as a result of self-assembling of capsid protein subunits, showed efficient delivery of siRNA to the tumor tissues in vivo, due to the RGD-mediated binding to integrin receptors overexpressed on tumor cells. Moreover, the prolonged in vivo circulation time of our siRNA/capsid nanocarrier complexes increased the potential to serve as siRNA carriers for optimal in vivo RNAi. These results provide an alternative approach to systemically deliver siRNA to the tumor sites as well as to enhance the stability of siRNA in vivo. Therefore, our results revealed the promising potential of our capsid nanocarrier system as a therapeutic siRNA carrier for cancer treatment.
URI
http://pubs.kist.re.kr/handle/201004/43876
ISSN
15438384
Appears in Collections:
KIST Publication > Article
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