Efficient siRNA delivery into tumor cells by p19-YSA fusion protein

Kyung Mi Choi, Ggon Lip Park, Kwang Yeon Hwang, Jeong Won Lee, Hyung Jun Ahn

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)763-773
Number of pages11
JournalMolecular Pharmaceutics
Volume10
Issue number2
DOIs
Publication statusPublished - 2013 Feb 4

Keywords

  • cytoplasmic delivery
  • ephrin mimetic peptide
  • recombinant protein
  • siRNA
  • tumor targeting

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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