title: Genetically modified Tomato aspermy virus 2b protein as a tumor-targeting siRNA delivery carrier.
abstract: In nature, there exist a wide range of dsRNA-binding proteins that have different binding modes for small interfering RNA (siRNA) as well as structural differences, and some of these proteins have potential as effective siRNA delivery carriers. In order to deliver siRNA into cancer cells, a dsRNA-binding 2b protein derived from Tomato aspermy virus was genetically modified by fusing the integrin-targeting RGD peptide to its C-terminus, and biosynthesized. The resulting 2b-RGD protein possesses distinct characteristics favorable for biomedical applications of siRNA: (i) high affinity for siRNA, (ii) siRNA protection against RNases in serum, (iii) low cytotoxicity compared to the polycationic polymers often employed in conventional siRNA carriers, (iv) specific binding to integrins on cancer cells, and the ability to pass through the cell membrane via endocytosis, and (v) the ability to facilitate cytosolic release of siRNA. Here, we demonstrate that the 2b-RGD/siRNA complexes have great potential as a tumor-targeting siRNA delivery carrier and suggest their possible therapeutic applications for cancer treatment.
authors: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul 136-791, South Korea.
authors: Eun Young
authors: EY
authors: Park
authors: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul 136-791, South Korea.
authors: Mihue
authors: M
authors: Jang
authors: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul 136-791, South Korea.
authors: Jong Hwan
authors: JH
authors: Kim
authors: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul 136-791, South Korea. Electronic address: hjahn@kist.re.kr.
authors: Hyung Jun
authors: HJ
authors: Ahn
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D055785:Gene Knockdown Techniques; D018014:Gene Transfer Techniques; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018551:Solanum lycopersicum / Q000821:virology*; D008297:Male; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology; D008856:Microscopy, Fluorescence; D010942:Plant Viruses / Q000235:genetics*; D020871:RNA Stability / Q000187:drug effects; D012330:RNA, Double-Stranded / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins
keywords: Cancer treatment; RNAi; Recombinant proteins; Tumor-targeting; siRNA delivery carrier