Choi, Kyung-mi Park, Ggon Lip Hwang, Kwang Yeon Lee, Jeong-Won Ahn, Hyung Jun 2024-01-20T13:02:34Z 2024-01-20T13:02:34Z 2021-09-01 2013-02 1543-8384 https://pubs.kist.re.kr/handle/201004/128398 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. English AMER CHEMICAL SOC SMALL INTERFERING RNAS IN-VIVO EPHA2 RECEPTOR GENE DELIVERY SYNTHETIC SIRNAS COATED PIT THERAPEUTICS CANCER 5-FLUOROURACIL CYTOTOXICITY Efficient siRNA Delivery into Tumor Cells by p19-YSA Fusion Protein Article 10.1021/mp300344p 1 MOLECULAR PHARMACEUTICS, v.10, no.2, pp.763 - 773 MOLECULAR PHARMACEUTICS 10 2 763 773 scie scopus 000314627400035 2-s2.0-84873363217 Medicine, Research & Experimental Pharmacology & Pharmacy Research & Experimental Medicine Pharmacology & Pharmacy Article SMALL INTERFERING RNAS IN-VIVO EPHA2 RECEPTOR GENE DELIVERY SYNTHETIC SIRNAS COATED PIT THERAPEUTICS CANCER 5-FLUOROURACIL CYTOTOXICITY siRNA cytoplasmic delivery recombinant protein tumor targeting ephrin mimetic peptide