Efficient siRNA Delivery into Tumor Cells by p19-YSA Fusion Protein

Title
Efficient siRNA Delivery into Tumor Cells by p19-YSA Fusion Protein
Authors
최경미박꽃잎황광연이정원안형준
Keywords
siRNA; delivery; p19; tumor; cytoplasmic delivery; recombinant protein; tumor targeting; ephrin mimetic peptide
Issue Date
2013-02
Publisher
Molecular pharmaceutics
Citation
VOL 10, NO 2, 763-773
Abstract
For the efficient cytoplasmic delivery of siRNA in a receptor-specific fashion, we designed a p19-YSA fusion protein composed of p19 RNA binding protein and ephrin mimetic peptide (YSA peptide). The resulting recombinant protein had the high affinity for EphA2 receptor overexpressed on cancer cells as well as the complexing ability with siRNA, thus leading to tumor-targeted delivery of siRNA. The buried structure of siRNA within p19-YSA/siRNA complexes allowed the bound siRNAs to be protected from the external RNases, resulting in the enhanced stability of siRNA in serum conditions. The p19-YSA carriers could complex with siRNA in a size-dependent and sequence-independent manner and showed the pH-dependent complexing/dissocation behaviors with siRNA. In contrast to electrostatic interaction-mediated siRNA delivery systems such as cationic polymers/siRNA or cationic polypeptides/siRNA complexes, the bound siRNA within p19-YSA/siRNA complexes showed enhanced stability against large polyanions found outside cells, due to the nanomolar levels of affinity. Here, we demonstrated the superior efficiency of p19-YSA/siRNA complexes in RFP gene silencing, compared to untreated cells. These results provide an alternative approach to enhance the stability of siRNA as well as to achieve the targeted siRNA delivery.
URI
http://pubs.kist.re.kr/handle/201004/46068
ISSN
15438384
Appears in Collections:
KIST Publication > Article
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