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Partial correction of endogenous DeltaF508 CFTR in human cystic fibrosis airway epithelia by spliceosome-mediated RNA trans-splicing.

Publication ,  Journal Article
Liu, X; Jiang, Q; Mansfield, SG; Puttaraju, M; Zhang, Y; Zhou, W; Cohn, JA; Garcia-Blanco, MA; Mitchell, LG; Engelhardt, JF
Published in: Nat Biotechnol
January 2002
Published version (DOI) Link to item

Spliceosome-mediated RNA trans-splicing (SMaRT) was investigated as a means for functionally correcting endogenous DeltaF508 cystic fibrosis transmembrane conductance regulator (CFTR) transcripts using in vitro human cystic fibrosis (CF) polarized airway epithelia and in vivo human CF bronchial xenografts. Recombinant adenovirus (Ad.CFTR-PTM) encoding a pre-therapeutic molecule (PTM) targeted to CFTR intron 9 corrected transepithelial cyclic AMP (cAMP)-sensitive short-circuit current (Isc) in DeltaF508 homozygous epithelia to a level 16% of that observed in normal human bronchial epithelia. Molecular analyses using RT-PCR and western blotting confirmed SMaRT-mediated partial correction of endogenous DeltaF508 messenger RNA (mRNA) transcripts and protein. In an in vivo model of DeltaF508 CF airway epithelia, human CF bronchial xenografts infected with Ad.CFTR-PTM also demonstrated partial correction of CFTR-mediated Cl- permeability at a level 22% of that seen in non-CF xenografts. These results provide functional evidence for SMaRT-mediated repair of mutant endogenous CFTR mRNA in intact polarized CF airway epithelial models.

Duke Scholars

Jonathan Allen Cohn
Author Jonathan Allen Cohn Medicine, Gastroenterology
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Published In

Nat Biotechnol

DOI

10.1038/nbt0102-47

ISSN

1087-0156

Publication Date

January 2002

Volume

20

Issue

1

Start / End Page

47 / 52

Location

United States

Related Subject Headings

  • Spliceosomes
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Messenger
  • RNA Splicing
  • Mutation
  • Molecular Sequence Data
  • Models, Genetic
  • Immunoblotting
  • Humans
  • Hela Cells
 

Citation

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MLA
NLM
Liu, X., Jiang, Q., Mansfield, S. G., Puttaraju, M., Zhang, Y., Zhou, W., … Engelhardt, J. F. (2002). Partial correction of endogenous DeltaF508 CFTR in human cystic fibrosis airway epithelia by spliceosome-mediated RNA trans-splicing. Nat Biotechnol, 20(1), 47–52. https://doi.org/10.1038/nbt0102-47
Liu, Xiaoming, Qinshi Jiang, S Gary Mansfield, M. Puttaraju, Yulong Zhang, Weihong Zhou, Jonathan A. Cohn, Mariano A. Garcia-Blanco, Lloyd G. Mitchell, and John F. Engelhardt. “Partial correction of endogenous DeltaF508 CFTR in human cystic fibrosis airway epithelia by spliceosome-mediated RNA trans-splicing.” Nat Biotechnol 20, no. 1 (January 2002): 47–52. https://doi.org/10.1038/nbt0102-47.
Liu X, Jiang Q, Mansfield SG, Puttaraju M, Zhang Y, Zhou W, et al. Partial correction of endogenous DeltaF508 CFTR in human cystic fibrosis airway epithelia by spliceosome-mediated RNA trans-splicing. Nat Biotechnol. 2002 Jan;20(1):47–52.
Liu, Xiaoming, et al. “Partial correction of endogenous DeltaF508 CFTR in human cystic fibrosis airway epithelia by spliceosome-mediated RNA trans-splicing.” Nat Biotechnol, vol. 20, no. 1, Jan. 2002, pp. 47–52. Pubmed, doi:10.1038/nbt0102-47.
Liu X, Jiang Q, Mansfield SG, Puttaraju M, Zhang Y, Zhou W, Cohn JA, Garcia-Blanco MA, Mitchell LG, Engelhardt JF. Partial correction of endogenous DeltaF508 CFTR in human cystic fibrosis airway epithelia by spliceosome-mediated RNA trans-splicing. Nat Biotechnol. 2002 Jan;20(1):47–52.

Published In

Nat Biotechnol

DOI

10.1038/nbt0102-47

ISSN

1087-0156

Publication Date

January 2002

Volume

20

Issue

1

Start / End Page

47 / 52

Location

United States

Related Subject Headings

  • Spliceosomes
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Messenger
  • RNA Splicing
  • Mutation
  • Molecular Sequence Data
  • Models, Genetic
  • Immunoblotting
  • Humans
  • Hela Cells