title: Chimeric capsid protein as a nanocarrier for siRNA delivery: stability and cellular uptake of encapsulated siRNA.
abstract: For the efficient cytoplasmic delivery of siRNA, we designed a chimeric capsid protein composed of a capsid shell, integrin targeting peptide, and p19 RNA binding protein. This recombinant protein assembled into a macromolecular container-like structure with capsid shell and provided a nanocarrier for siRNA delivery. Our capsid nanocarriers had dual affinity both for siRNA within the interior and integin receptors on the exterior, and the capsid shell structure allowed the encapsulated siRNAs to be protected from the external nucleases, leading to the enhanced stability of siRNA in serum conditions. The capsid nanocarriers could complex with siRNA in a size-dependent and sequence-independent manner and showed the pH-dependent complexing/dissocation behaviors with siRNA. Moreover, RGD peptides on the exterior surface of the capsid shell enabled the capsid nanocarriers to deliver siRNA into the cytosol of the target cells. Here, we demonstrated the superior efficiency of our siRNA/capsid nanocarrier complexes in RFP gene silencing, compared to untreated cells. These results provide an alternative approach to enhancing the stability of siRNA as well as to achieving targeted siRNA delivery.
authors: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk-Gu, Seoul 136-791, South Korea.
authors: Kyung-mi
authors: KM
authors: Choi
authors: Seung-Hye
authors: SH
authors: Choi
authors: Hyesung
authors: H
authors: Jeon
authors: In-San
authors: IS
authors: Kim
authors: Hyung Jun
authors: HJ
authors: Ahn
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D036022:Capsid Proteins / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D002214:Capsules; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D020868:Gene Silencing; D006515:Hepatitis B virus / Q000737:chemistry; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D049329:Nanostructures / Q000737:chemistry* / Q000633:toxicity; D011487:Protein Conformation; D021381:Protein Transport; D020871:RNA Stability; D034741:RNA, Small Interfering / Q000097:blood / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D000097573:Red Fluorescent Protein
chemical_list: D036022:Capsid Proteins; D002214:Capsules; D004337:Drug Carriers; D008164:Luminescent Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D000097573:Red Fluorescent Protein