Inhibition of simian virus 40 large tumor antigen expression in human fetal glial cells by an antisense oligodeoxynucleotide delivered by the JC virus-like particle.
Human JC virus (JCV) is a neurotropic virus, and the etiological agent of progressive multifocal leukoencephalopathy (PML), a fatal neurological disease. Because of its natural infection tropism, it is possible to use the JCV capsid as a gene-transducing vector for therapeutic purposes in neurological disorders. In the current study, a recombinant JCV virus-like particle (VLP) was generated and purified from yeast. VLP was able to accommodate and protect DNA molecules of up to approximately 2000 bp in length. VLP was able to package and deliver an antisense oligodeoxynucleotide (AS-ODN) against simian virus 40 (SV40) large tumor antigen (LT) into SV40-transformed human fetal glial (SVG) cells in order to inhibit expression of the oncoprotein. Subsequently, apoptosis of VLP-AS-ODN-treated cells was demonstrated after the blocking of LT expression. In addition, JCV VLP was able to deliver ODN into human astrocytoma, neuroblastoma, and glioblastoma cells with high efficiency. In vivo delivery of ODN into a human neuroblastoma tumor nodule by VLP was also demonstrated. These findings suggest that JCV VLP is a gene delivery vector with potential therapeutic use for human neurological disorders.
Wang
Meilin
M
Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan.
Tsou
Tsung-Hsuan
TH
Chen
Li-Sheng
LS
Ou
Wei-Chih
WC
Chen
Pei-Lain
PL
Chang
Chi-Fang
CF
Fung
Chiung-Yau
CY
Chang
Deching
D
D017304:Annexin A5 / Q000494:pharmacology; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007577:JC Virus / Q000235:genetics*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000628:therapy*; D008858:Microscopy, Phase-Contrast; D009422:Nervous System Diseases / Q000628:therapy; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism*; D009841:Oligonucleotides / Q000737:chemistry / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000235:genetics* / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011419:Propidium / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D014466:Ultraviolet Rays
D017304:Annexin A5; D000952:Antigens, Polyomavirus Transforming; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D011419:Propidium; D004247:DNA