Filovirus-pseudotyped lentiviral vector can efficiently and stably transduce airway epithelia in vivo.
Traditional gene therapy vectors have demonstrated limited utility for treatment of chronic lung diseases such as cystic fibrosis (CF). Herein we describe a vector based on a Filovirus envelope protein-pseudotyped HIV vector, which we chose after systematically evaluating multiple strategies. The vector efficiently transduces intact airway epithelium from the apical surface, as demonstrated in both in vitro and in vivo model systems. This shows the potential of pseudotyping in expanding the utility of lentiviral vectors. Pseudotyped lentiviral vectors may hold promise for the treatment of CF.
Kobinger
G P
GP
Institute for Human Gene Therapy and Department of Molecular and Cellular Engineering, University of Pennsylvania Health System, Philadelphia, PA 19104, USA.
Weiner
D J
DJ
Yu
Q C
QC
Wilson
J M
JM
D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics / Q000502:physiology; D016764:Cell Polarity; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000235:genetics / Q000628:therapy; D004285:Dogs; D029043:Ebolavirus / Q000145:classification / Q000235:genetics / Q000502:physiology; D004848:Epithelium / Q000378:metabolism* / Q000821:virology; D016563:Filoviridae / Q000145:classification / Q000235:genetics* / Q000502:physiology* / Q000648:ultrastructure; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics*; D006678:HIV / Q000235:genetics* / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000821:virology; D029024:Marburgvirus / Q000235:genetics / Q000502:physiology; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000502:physiology; D012137:Respiratory System / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D014132:Trachea / Q000166:cytology / Q000378:metabolism / Q000821:virology; D014161:Transduction, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism
C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins