Feline immunodeficiency virus vectors persistently transduce nondividing airway epithelia and correct the cystic fibrosis defect

Wang, Guoshun; Slepushkin, Vladimir; Zabner, Joseph; Keshavjee, Shaf; Johnston, James D.; Sauter, Sybille L.; Jolly, Doug J.; Dubensky, Thomas W.; Davidson, Beverly L.; McCray, Paul B.

doi:10.1172/jci8390

Cited by 157 publications

(168 citation statements)

References 60 publications

Supporting

Mentioning

165

Contrasting

Order By: Relevance

“…FIV vectors have been used to target cells in the brain, eye, airway, hematopoietic system, liver, muscle and pancreas [8,15,16,19,[45][46][47][48][49][50][51][52][53][54][55][56][57]. Exceptional results in the central nervous system have been obtained [47].…”

Section: Introductionmentioning

confidence: 99%

“…Exceptional results in the central nervous system have been obtained [47]. Although controlled infectivity and efficacy comparisons on a per particle basis have been lacking, in several systems, FIV vectors have produced excellent levels of gene transfer and expression in cultured human organs [45,55,56]. In the one direct comparison using transducing unit-normalized preparations (trabecular meshwork transduction in an organ perfusion model used for preclinical glaucoma gene therapy research), FIV and HIV-1 vectors produced equivalent results in human eyes [55].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

FIV: from lentivirus to lentivector

Saenz

Poeschla

2004

J. Gene Med.

View full text Add to dashboard Cite

SummaryMolecular virological understanding of the feline immunodeficiency virus (FIV) life cycle is increasing, facilitating rational derivation of improved vectors from this non-primate lentivirus. The packaging signal has been mapped, a central DNA flap has been identified, and class I integrase mutants have been validated. Vector systems with improved effectiveness and safety profiles are being applied by a number of laboratories in several pre-clinical models, with demonstrated efficacy in human tissues. The comparative lentivirological research that facilitates FIV vector development may also yield insights into the still enigmatic molecular basis for a signature lentiviral property with pathogenetic and therapeutic importance: permanent transgene integration in non-dividing cells. This review discusses virological aspects of lentiviral vector development, as well as some recent controversies and applications.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

FIV: from lentivirus to lentivector

Saenz

Poeschla

2004

J. Gene Med.

View full text Add to dashboard Cite

show abstract

“…To achieve evolutionary success, viruses may alter or compromise each of these steps to reduce the efficiency of infection and achieve a balance between the production of viruses that spread, but do not cause, host (and hence virus) extinction. This concept is strikingly illustrated by the inefficiency, and consequent lack of therapeutic end points, of gene transfer vectors based on respiratory viruses for respiratory diseases (3)(4)(5)(6). A better understanding of evolutionary principles governing natural viral evolution will drive more advanced methods to successfully engineer novel virus-based gene therapeutics.…”

mentioning

confidence: 99%

Directed evolution of adeno-associated virus to an infectious respiratory virus

Excoffon

Koerber²,

Dickey

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

149

180

View full text Add to dashboard Cite

Respiratory viruses evolve to maintain infectivity levels that permit spread yet prevent host and virus extinction, resulting in surprisingly low infection rates. Respiratory viruses harnessed as gene therapy vectors have illustrated this limitation. We used directed evolution in an organotypic human airway model to generate a highly infectious adeno-associated virus. This virus mediated gene transfer more than 100-fold better than parental strains and corrected the cystic fibrosis epithelial Cl ؊ transport defect. Thus, under appropriate selective pressures, viruses can evolve to be more infectious than observed in nature, a finding that holds significant implications for designing vectors for gene therapy and for understanding emerging pathogens.

show abstract

“…As a model for integration following hepatocyte transduction (12,13,21), we cloned, sequenced, and mapped FIV vector integration sites in human hepatoma cells. Vesicular stomatitis virus G protein-pseudotyped FIV encoding enhanced green fluorescence protein (eGFP) driven by a cytomegalovirus promoter/enhancer was produced as described previously (11,25). HepG2 cells (HB-8065; ATCC, Rockville, MD) were transduced at a multiplicity of infection of ϳ1.…”

mentioning

confidence: 99%