title: Recombinant VLP-Z of JC Polyomavirus: A Novel Vector for Targeting Gene Delivery.
abstract: Virus-like particle (VLP) of JC polyomavirus (JCPyV) is capable of packaging and delivering exogenous DNA into human cells and can be used for mediating therapeutic gene expression. However, many human cells express the JCPyV receptor. Thus, wild-type VLP can transduce a wide range of human cells nonspecifically. This study tested the feasibility of using a modified VLP with a IgG binding domain (Z domain) of protein A in its capsid for targeted gene delivery. The Z domain of protein A isolated from the membrane of Staphylococcus aureus was inserted into the NH3-terminus of VP1, the major JCPyV capsular protein. The recombinant VLP-Z was produced using Escherichia coli. Electron-microscopic analysis showed that VLP-Z has a viral-like structure. A hemagglutination test showed that VLP-Z has hemagglutination activity. VP(1) was detected in the nuclei of HeLa cells by immunostaining after VLP-Z inoculation, suggesting that VLP-Z is viable and can enter the cell nucleus. Inoculating HeLa cells with pEGFP-N(1) plasmid packaged in VLP-Z has resulted in enhanced green fluorescent protein expression in the cells. In addition, a binding assay showed that VLP-Z was able to bind IgG through the interaction of the Z domain in VLP-Z and IgG. These data suggest that VLP-Z could be armed with cell-specific antibody and be used to deliver therapeutic genes to target cells.
authors.affiliation: Department of Neurology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Yong-Ning
authors.initials: YN
authors.lastname: Deng
authors.forename: Jun-Yan
authors.initials: JY
authors.lastname: Zeng
authors.forename: Hua
authors.initials: H
authors.lastname: Su
authors.forename: Qiu-Min
authors.initials: QM
authors.lastname: Qu
mesh_terms: D036022:Capsid Proteins / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007577:JC Virus / Q000235:genetics* / Q000648:ultrastructure; D010957:Plasmids / Q000235:genetics; D013205:Staphylococcal Protein A / Q000235:genetics; D013211:Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism; D014771:Virion / Q000648:ultrastructure
chemical_list: D036022:Capsid Proteins; D007074:Immunoglobulin G; D013205:Staphylococcal Protein A; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins