Non-invasive liposome-mediated gene delivery can correct the ion transport defect in cystic fibrosis mutant mice

E. W. Alton; P. G. Middleton; N. J. Caplen; S. N. Smith; D. M. Steel; F. M. Munkonge; P. K. Jeffery; D. M. Geddes; S. L. Hart; R. Williamson; K. I. Fasold; A. D. Miller; P. Dickinson; B. J. Stevenson; McLachlan G.; J. R. Dorin; D. J. Porteous

Non-invasive liposome-mediated gene delivery can correct the ion transport defect in cystic fibrosis mutant mice

E. W. Alton, P. G. Middleton, N. J. Caplen, S. N. Smith, D. M. Steel, F. M. Munkonge, P. K. Jeffery, D. M. Geddes, S. L. Hart, R. Williamson, K. I. Fasold, A. D. Miller, P. Dickinson, B. J. Stevenson, McLachlan G., J. R. Dorin, D. J. Porteous

Research output: Contribution to journal › Article › peer-review

Abstract

We report gene transfer to the Edinburgh insertional mutant mouse (cf/cf), delivering CFTR cDNA-liposome complexes into the airways by nebulization. We show full restoration of cAMP related chloride responses in some animals and demonstrate, in the same tissues, human CFTR cDNA expression. Overall, a range of correction was seen with restoration of about 50% of the deficit between wild type mice and untreated cf/cf controls. We report modest correction in the intestinal tract following direct instillation and provide initial encouraging safety data for both the respiratory and intestinal tract following the liposome mediated gene delivery. The non-viral nature and potentially lower immunogenicity of DNA-liposomes suggest that this may offer a therapeutic alternative to adenoviral therapies.

Original language	English
Pages (from-to)	135-142
Number of pages	8
Journal	Nature Genetics
Volume	5
Issue number	2
Publication status	Published - 1993

Keywords

Animals Base Sequence Biological Transport/genetics Cystic Fibrosis/genetics/*therapy Cystic Fibrosis Transmembrane Conductance Regulator DNA, Complementary *Gene Therapy Genes, Reporter Humans Intestines Ions Liposomes Membrane Proteins/*genetics Mice Mice, Mutant Strains Molecular Sequence Data Nebulizers and Vaporizers Oligodeoxyribonucleotides

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Alton, E. W., Middleton, P. G., Caplen, N. J., Smith, S. N., Steel, D. M., Munkonge, F. M., Jeffery, P. K., Geddes, D. M., Hart, S. L., Williamson, R., Fasold, K. I., Miller, A. D., Dickinson, P., Stevenson, B. J., G., M., Dorin, J. R., & Porteous, D. J. (1993). Non-invasive liposome-mediated gene delivery can correct the ion transport defect in cystic fibrosis mutant mice. Nature Genetics, 5(2), 135-142. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7504552

@article{8239024a23594dd0a09c297be4222e7f,

title = "Non-invasive liposome-mediated gene delivery can correct the ion transport defect in cystic fibrosis mutant mice",

abstract = "We report gene transfer to the Edinburgh insertional mutant mouse (cf/cf), delivering CFTR cDNA-liposome complexes into the airways by nebulization. We show full restoration of cAMP related chloride responses in some animals and demonstrate, in the same tissues, human CFTR cDNA expression. Overall, a range of correction was seen with restoration of about 50% of the deficit between wild type mice and untreated cf/cf controls. We report modest correction in the intestinal tract following direct instillation and provide initial encouraging safety data for both the respiratory and intestinal tract following the liposome mediated gene delivery. The non-viral nature and potentially lower immunogenicity of DNA-liposomes suggest that this may offer a therapeutic alternative to adenoviral therapies.",

keywords = "Animals Base Sequence Biological Transport/genetics Cystic Fibrosis/genetics/*therapy Cystic Fibrosis Transmembrane Conductance Regulator DNA, Complementary *Gene Therapy Genes, Reporter Humans Intestines Ions Liposomes Membrane Proteins/*genetics Mice Mice, Mutant Strains Molecular Sequence Data Nebulizers and Vaporizers Oligodeoxyribonucleotides",

author = "Alton, {E. W.} and Middleton, {P. G.} and Caplen, {N. J.} and Smith, {S. N.} and Steel, {D. M.} and Munkonge, {F. M.} and Jeffery, {P. K.} and Geddes, {D. M.} and Hart, {S. L.} and R. Williamson and Fasold, {K. I.} and Miller, {A. D.} and P. Dickinson and Stevenson, {B. J.} and McLachlan G. and Dorin, {J. R.} and Porteous, {D. J.}",

note = "Oct Non-invasive liposome-mediated gene delivery can correct the ion transport defect in cystic fibrosis mutant mice Journal Article Research Support, Non-U.S. Gov't United states eng",

year = "1993",

language = "English",

volume = "5",

pages = "135--142",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "2",

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Alton, EW, Middleton, PG, Caplen, NJ, Smith, SN, Steel, DM, Munkonge, FM, Jeffery, PK, Geddes, DM, Hart, SL, Williamson, R, Fasold, KI, Miller, AD, Dickinson, P, Stevenson, BJ, G., M, Dorin, JR & Porteous, DJ 1993, 'Non-invasive liposome-mediated gene delivery can correct the ion transport defect in cystic fibrosis mutant mice', Nature Genetics, vol. 5, no. 2, pp. 135-142. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7504552>

TY - JOUR

T1 - Non-invasive liposome-mediated gene delivery can correct the ion transport defect in cystic fibrosis mutant mice

AU - Alton, E. W.

AU - Middleton, P. G.

AU - Caplen, N. J.

AU - Smith, S. N.

AU - Steel, D. M.

AU - Munkonge, F. M.

AU - Jeffery, P. K.

AU - Geddes, D. M.

AU - Hart, S. L.

AU - Williamson, R.

AU - Fasold, K. I.

AU - Miller, A. D.

AU - Dickinson, P.

AU - Stevenson, B. J.

AU - G., McLachlan

AU - Dorin, J. R.

AU - Porteous, D. J.

N1 - Oct Non-invasive liposome-mediated gene delivery can correct the ion transport defect in cystic fibrosis mutant mice Journal Article Research Support, Non-U.S. Gov't United states eng

PY - 1993

Y1 - 1993

N2 - We report gene transfer to the Edinburgh insertional mutant mouse (cf/cf), delivering CFTR cDNA-liposome complexes into the airways by nebulization. We show full restoration of cAMP related chloride responses in some animals and demonstrate, in the same tissues, human CFTR cDNA expression. Overall, a range of correction was seen with restoration of about 50% of the deficit between wild type mice and untreated cf/cf controls. We report modest correction in the intestinal tract following direct instillation and provide initial encouraging safety data for both the respiratory and intestinal tract following the liposome mediated gene delivery. The non-viral nature and potentially lower immunogenicity of DNA-liposomes suggest that this may offer a therapeutic alternative to adenoviral therapies.

AB - We report gene transfer to the Edinburgh insertional mutant mouse (cf/cf), delivering CFTR cDNA-liposome complexes into the airways by nebulization. We show full restoration of cAMP related chloride responses in some animals and demonstrate, in the same tissues, human CFTR cDNA expression. Overall, a range of correction was seen with restoration of about 50% of the deficit between wild type mice and untreated cf/cf controls. We report modest correction in the intestinal tract following direct instillation and provide initial encouraging safety data for both the respiratory and intestinal tract following the liposome mediated gene delivery. The non-viral nature and potentially lower immunogenicity of DNA-liposomes suggest that this may offer a therapeutic alternative to adenoviral therapies.

KW - Animals Base Sequence Biological Transport/genetics Cystic Fibrosis/genetics/therapy Cystic Fibrosis Transmembrane Conductance Regulator DNA, Complementary Gene Therapy Genes, Reporter Humans Intestines Ions Liposomes Membrane Proteins/genetics Mice Mice,

M3 - Article

VL - 5

SP - 135

EP - 142

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 2

ER -

Non-invasive liposome-mediated gene delivery can correct the ion transport defect in cystic fibrosis mutant mice

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Keywords

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