Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells

Rich, Devra P.; Anderson, Matthew P.; Gregory, Richard J.; Cheng, Seng H.; Paul, Sucharita; Jefferson, Douglas M.; McCann, John D.; Klinger, Katherine W.; Smith, Alan E.; Welsh, Michael J.

doi:10.1038/347358a0

Cited by 628 publications

(245 citation statements)

References 29 publications

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“…3,11 However, it has been suggested that certain applications of pulmonary gene therapy might require only low levels of expression for therapeutic effect. For example, in cystic fibrosis there is evidence both in vitro 29 and in vivo 30 indicating that low levels of CFTR expression could re-establish physiological ion transport. Thus some form of enhanced transfer of naked DNA may be a viable therapeutic approach for certain disorders afflicting the respiratory epithelium.…”

Section: Discussionmentioning

confidence: 99%

The effect of synthetic surfactant Exosurf on gene transfer in mouse lung in vivo

et al. 1998

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Gene transfer in the lung holds promise for the treatment for 5 days thereafter. When DNA was delivered in a 50% of diseases such as pulmonary fibrosis, cystic fibrosis and suspension of Exosurf, the expression of either CAT or asthma. Pulmonary surfactant has been reported to Luc was significantly reduced by 89.6 ± 1.4% and enhance expression from endobronchial, adenovirus-82.7 ± 10.5%, respectively. The decrease in Luc mediated gene transfer in experimental animals. This study expression was closely correlated (r = 0.99, P Ͻ 0.001) to examines the effect of exogenous synthetic surfactant log concentration of surfactant in the plasmid buffer sol-(Exosurf) on gene expression from naked plasmid DNA ution (IC 50 = 8.6%). CAT expression was not altered when administered endobronchially to adult mice. Transfection surfactant was administered either 2 h before or after plasefficiency was evaluated by quantifying the expression of mid DNA instillation. Examination of the components of chloramphenicol acetyltransferase (CAT) and luciferase Exosurf revealed that two compounds, DPPC and tylox-(Luc) genes in the lung. Endobronchial administration of apol, showed inhibitory effects on CAT expression. Howeither CAT or Luc expression plasmid DNA resulted in ever, the inhibition caused by Exosurf appeared greater detectable concentrations of each reporter protein. CAT than that of either component. Our results suggest that the expression from plasmid DNA was monitored after endolung surfactant is a barrier to transfection of the endobronchial administration with the maximal expression bronchial airway and may be partly responsible for the low observed at 3-5 days after administration and decreasing expression of exogenous DNA in vivo in the bronchial tree.

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Section: Discussionmentioning

confidence: 99%

The effect of synthetic surfactant Exosurf on gene transfer in mouse lung in vivo

et al. 1998

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“…The effect of HCO 3 − in triggering downstream signaling requires CFTR (cystic fibrosis transmembrane conductance regulator), a cAMP-activated anion channel known to conduct Cl − [29,30] and HCO 3 − [31], as the necessary HCO 3 − transport mechanism, either directly or indirectly [28,32]. This suggests that high HCO 3 − concentration may act as an environmental stimulus in initiating cellular responses through CFTR-mediated entry.…”

Section: Hcomentioning

confidence: 99%

CFTR mediates bicarbonate-dependent activation of miR-125b in preimplantation embryo development

et al. 2012

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“…It is known that CFTR function can be restored in CF cell lines by delivering full length wild-type CFTR cDNA. [16][17][18][19][20] Studies in CF mouse models 21,22 and in CF patients [23][24][25] suggest that similar correction may also be possible in vivo. However, the conventional approach of delivering full length wild-type CFTR cDNA has encountered problems as the cDNA is at or slightly larger than the packaging size of the leading vector for CF gene therapy.…”

Section: Introductionmentioning

confidence: 99%

Repair of CFTR mRNA by spliceosome-mediated RNA trans-splicing

Mansfield¹,

Kole

Puttaraju³

et al. 2000

Gene Ther

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Most messenger RNA precursors (pre-mRNA) undergo cissplicing in which introns are excised and the adjoining exons from a single pre-mRNA are ligated together to form mature messenger RNA. This reaction is driven by a complex known as the spliceosome. Spliceosomes can also combine sequences from two independently transcribed pre-mRNAs in a process known as trans-splicing. Spliceosome-mediated RNA trans-splicing (SMaRT) is an emerging technology in which RNA pre-therapeutic molecules (PTMs) are designed to recode a specific pre-mRNA by suppressing cis-splicing while enhancing trans-splicing between the PTM and its premRNA target. This study examined the feasibility of SMaRT as a potential therapy for genetic diseases to correct mutations using cystic fibrosis (CF) as an example. We used several versions of a cystic fibrosis transmembrane conduc-

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Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells

Cited by 628 publications

References 29 publications

The effect of synthetic surfactant Exosurf on gene transfer in mouse lung in vivo

The effect of synthetic surfactant Exosurf on gene transfer in mouse lung in vivo

CFTR mediates bicarbonate-dependent activation of miR-125b in preimplantation embryo development

Repair of CFTR mRNA by spliceosome-mediated RNA trans-splicing

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