Delivery of herpes simplex virus vectors through liposome formulation.
Viral vectors have been widely used as gene delivery vehicles for both experimental and clinical investigations. Although these vectors are capable of achieving high gene transduction efficiency in vitro, one of the major limitations facing the therapeutic viral vectors is that the preexisting host anti-vector immunity can substantially reduce their transduction efficiency in vivo. This is especially of concern when the therapeutic remedy requires repeated systemic administration. Here we report the delivery of herpes simplex virus (HSV) derived vectors through liposome formulation. In these studies, we have prepared HSV vectors in three different forms for liposome formulation: purified viral DNA (obtained from a bacterial artificial chromosome containing an infectious HSV genome), HSV capsids, and intact viral particles. All three forms of HSV were readily transfected into cultured cells and infectious virus was efficiently generated. Furthermore, introduction of HSV vectors as DNA/liposome complexes improved in vivo transduction efficiency, by effectively evading the host anti-HSV immunity during systemic administration. We conclude that viral vectors such as HSV can be systemically delivered through liposome formulation for safe and repeated administration for gene transduction or oncolytic purposes.
Fu
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Center for Cell and Gene Therapy, Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Zhang
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D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002213:Capsid / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D004279:DNA, Viral / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D049452:Green Fluorescent Proteins; D008081:Liposomes / Q000008:administration & dosage / Q000378:metabolism*; D008163:Luminescent Measurements; D008164:Luminescent Proteins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D018139:Simplexvirus / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D014161:Transduction, Genetic / Q000379:methods*; D014162:Transfection
D004279:DNA, Viral; D008081:Liposomes; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D000469:Alkaline Phosphatase