Apical barriers to airway epithelial cell gene transfer with amphotropic retroviral vectors

Wang, G; Williams, Greg; Xia, Haibin; Hickey, Melissa; Shao, Jun Peng; Bl, Davidson; McCray, Paul B.

doi:10.1038/sj.gt.3301714

Cited by 22 publications

(15 citation statements)

References 42 publications

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“…These data suggest that in polarized cells, access to low-pH endosomal compartments from either the apical or basolateral surface results in effective gene transfer. We previously reported that gene transfer with Ampho-FIV from the apical surface was ineffective despite evidence of receptor expression (53). Therefore, targeting receptors that use low-pH endosome entry pathways may be more productive in polarized epithelia.…”

Section: Discussionmentioning

confidence: 99%

Persistent Gene Expression in Mouse Nasal Epithelia following Feline Immunodeficiency Virus-Based Vector Gene Transfer

Sinn

Burnight

Hickey

et al. 2005

J Virol

101

130

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Gene transfer development for treatment or prevention of cystic fibrosis lung disease has been limited by the inability of vectors to efficiently and persistently transduce airway epithelia. Influenza A is an enveloped virus with natural lung tropism; however, pseudotyping feline immunodeficiency virus (FIV)-based lentiviral vector with the hemagglutinin envelope protein proved unsuccessful. Conversely, pseudotyping FIV with the envelope protein from influenza D (Thogoto virus GP75) resulted in titers of 10 6 transducing units (TU)/ml and conferred apical entry into well-differentiated human airway epithelial cells. Baculovirus GP64 envelope glycoproteins share sequence identity with influenza D GP75 envelope glycoproteins. Pseudotyping FIV with GP64 from three species of baculovirus resulted in titers of 10 7 to 10 9 TU/ml. Of note, GP64 from Autographa californica multicapsid nucleopolyhedrovirus resulted in high-titer FIV preparations (ϳ10 9 TU/ml) and conferred apical entry into polarized primary cultures of human airway epithelia. Using a luciferase reporter gene and bioluminescence imaging, we observed persistent gene expression from in vivo gene transfer in the mouse nose with A. californica GP64-pseudotyped FIV (AcGP64-FIV). Longitudinal bioluminescence analysis documented persistent expression in nasal epithelia for ϳ1 year without significant decline. According to histological analysis using a LacZ reporter gene, olfactory and respiratory epithelial cells were transduced. In addition, methylcellulose-formulated AcGP64-FIV transduced mouse nasal epithelia with much greater efficiency than similarly formulated vesicular stomatitis virus glycoprotein-pseudotyped FIV. These data suggest that AcGP64-FIV efficiently transduces and persistently expresses a transgene in nasal epithelia in the absence of agents that disrupt the cellular tight junction integrity.

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Section: Discussionmentioning

confidence: 99%

Persistent Gene Expression in Mouse Nasal Epithelia following Feline Immunodeficiency Virus-Based Vector Gene Transfer

Sinn

Burnight

Hickey

et al. 2005

J Virol

101

130

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“…The normal physiological barriers to apical cell entry imposed by the cell glycocalyx, cilia and the mucous layer are major contributing factors preventing efficient gene transfer to the airway epithelia. 23,24 These barriers are even less penetrable in CF patients with manifest lung disease due to the excessive and sticky bronchial secretions. This led us and others to investigate the prospects of fetal gene delivery aiming to achieve a more effective transduction of the airway epithelia, avoid immune sensitization against vector and transgene, and prevent early-onset tissue damage.…”

Section: Discussionmentioning

confidence: 99%

Widespread and efficient marker gene expression in the airway epithelia of fetal sheep after minimally invasive tracheal application of recombinant adenovirus in utero

et al. 2003

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“…In the liver, PiT-1 and PiT-2 localize to the basolateral membrane in hepatocytes (35), whereas in airway epithelial cells PiT-2 is expressed both apically and basolaterally (115). In P i -secreting glands, such as the lactating mammary gland (90) and ruminant parotid gland (105), PiT proteins may provide basolateral uptake of P i from the blood for subsequent secretion into the lumen through an as yet unknown mechanism.…”

Section: /P I Cotransporter Familymentioning

confidence: 99%

Phosphate transporters: a tale of two solute carrier families

Virkki¹,

Biber²,

Murer³

et al. 2007

American Journal of Physiology-Renal Physiology

219

227

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Phosphate is an essential component of life and must be actively transported into cells against its electrochemical gradient. In vertebrates, two unrelated families of Na+-dependent Pitransporters carry out this task. Remarkably, the two families transport different Pispecies: whereas type II Na+/Picotransporters (SCL34) prefer divalent HPO42−, type III Na+/Picotransporters (SLC20) transport monovalent H2PO4−. The SCL34 family comprises both electrogenic and electroneutral members that are expressed in various epithelia and other polarized cells. Through regulated activity in apical membranes of the gut and kidney, they maintain body Pihomeostasis, and in salivary and mammary glands, liver, and testes they play a role in modulating the Picontent of luminal fluids. The two SLC20 family members PiT-1 and PiT-2 are electrogenic and ubiquitously expressed and may serve a housekeeping role for cell Pihomeostasis; however, also more specific roles are emerging for these transporters in, for example, bone mineralization. In this review, we focus on recent advances in the characterization of the transport kinetics, structure-function relationships, and physiological implications of having two distinct Na+/Picotransporter families.

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Apical barriers to airway epithelial cell gene transfer with amphotropic retroviral vectors

Cited by 22 publications

References 42 publications

Persistent Gene Expression in Mouse Nasal Epithelia following Feline Immunodeficiency Virus-Based Vector Gene Transfer

Persistent Gene Expression in Mouse Nasal Epithelia following Feline Immunodeficiency Virus-Based Vector Gene Transfer

Widespread and efficient marker gene expression in the airway epithelia of fetal sheep after minimally invasive tracheal application of recombinant adenovirus in utero

Phosphate transporters: a tale of two solute carrier families

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