Journal article
Enhanced Gene Expression Conferred by Stepwise Modification of a Nonprimate Lentiviral Vector
Human gene therapy, Vol.18(12), pp.1244-1252
2007
DOI: 10.1089/hum.2006.127
PMID: 18052720
Abstract
The practical application of gene transfer as a treatment for genetic diseases such as cystic fibrosis or hemophilia has been hindered, in part, by low efficiencies of vector delivery and transgene expression. We demonstrated that a feline immunodeficiency virus (FIV)-based lentiviral vector pseudotyped with the envelope glycoprotein from the baculovirus Autographa californica (GP64) efficiently transduces and persistently expresses a reporter gene in respiratory epithelium in the absence of agents that disrupt cellular tight junction integrity. GP64-pseudotyped FIV also efficiently transduced murine hepatocytes after tail vein delivery. To improve the FIV-based vector, we tested the contribution of a series of modifications to luciferase expression in vitro and in vivo. These modifications included the addition of spleen necrosis virus U5 (SNV U5) and mutation of the major splice donor and gag start codon located in the packaging region of the FIV transgene plasmid. After vector modification, we observed significantly enhanced expression of luciferase in respiratory epithelia after nasal application and in the liver after tail vein delivery. In addition, we observed significantly enhanced human factor VIII production after tail vein delivery. These sequential modifications provide an improved FIV lentivirus platform for gene therapy applications and may be applied to other retroviral vectors.
Details
- Title: Subtitle
- Enhanced Gene Expression Conferred by Stepwise Modification of a Nonprimate Lentiviral Vector
- Creators
- Patrick L SINN - Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United StatesJessica D GOREHAM-VOSS - Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United StatesAriadna C ARIAS - Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United StatesMelissa A HICKEY - Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United StatesWendy MAURY - Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United StatesC. P CHIKKANNA-GOWDA - Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United StatesPaul B MCCRAY - Program in Gene Therapy, Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States
- Resource Type
- Journal article
- Publication Details
- Human gene therapy, Vol.18(12), pp.1244-1252
- Publisher
- Liebert
- DOI
- 10.1089/hum.2006.127
- PMID
- 18052720
- ISSN
- 1043-0342
- eISSN
- 1557-7422
- Language
- English
- Date published
- 2007
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984083873802771
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