Optimizing aerosol gene delivery and expression in the ovine lung

G. McLachlan; A. Baker; P. Tennant; C. Gordon; C. Vrettou; L. Renwick; R. Blundell; S. H. Cheng; R. K. Scheule; L. Davies; H. Painter; R. L. Coles; A. E. Lawton; C. Marriott; D. R. Gill; S. C. Hyde; U. Griesenbach; E. W. Alton; A. C. Boyd; D. J. Porteous; D. D. Collie

Optimizing aerosol gene delivery and expression in the ovine lung

G. McLachlan, A. Baker, P. Tennant, C. Gordon, C. Vrettou, L. Renwick, R. Blundell, S. H. Cheng, R. K. Scheule, L. Davies, H. Painter, R. L. Coles, A. E. Lawton, C. Marriott, D. R. Gill, S. C. Hyde, U. Griesenbach, E. W. Alton, A. C. Boyd, D. J. PorteousD. D. Collie

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

Abstract / Description of output

We have developed the sheep as a large animal model for optimizing cystic fibrosis gene therapy protocols. We administered aerosolized gene transfer agents (GTAs) to the ovine lung in order to test the delivery, efficacy, and safety of GTAs using a clinically relevant nebulizer. A preliminary study demonstrated GTA distribution and reporter gene expression throughout the lung after aerosol administration of plasmid DNA (pDNA):GL67 and pDNA:PEI complexes. A more comprehensive study examined the dose-response relationship for pDNA:PEI and assessed the influence of adjunct therapeutic agents. We found that the sheep model can differentiate between doses of GTA and that the anticholinergic, glycopyrrolate, enhanced transgene expression. Dose-related toxicity of GTA was reduced by aerosol administration compared to direct instillation. This large animal model will allow us to move toward clinical studies with greater confidence.

Original language	English
Pages (from-to)	348-354
Number of pages	7
Journal	Molecular Therapy
Volume	15
Issue number	2
Publication status	Published - 2007

Keywords / Materials (for Non-textual outputs)

Animals Chloramphenicol O-Acetyltransferase/genetics/metabolism Female Gene Expression Gene Transfer Techniques/adverse effects/*instrumentation Genes, Reporter/genetics Genetic Vectors/*genetics Lung/*metabolism Lung Diseases/etiology/pathology Male *Nebulizers and Vaporizers Recombinant Fusion Proteins/genetics/metabolism Sheep

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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17235313

Optimising delivery and analysis of gene transfer in the sheep lung
Gerry McLachlan (Speaker)
26 Oct 2008 → 28 Oct 2008
Activity: Academic talk or presentation types › Invited talk

Cite this

McLachlan, G., Baker, A., Tennant, P., Gordon, C., Vrettou, C., Renwick, L., Blundell, R., Cheng, S. H., Scheule, R. K., Davies, L., Painter, H., Coles, R. L., Lawton, A. E., Marriott, C., Gill, D. R., Hyde, S. C., Griesenbach, U., Alton, E. W., Boyd, A. C., ... Collie, D. D. (2007). Optimizing aerosol gene delivery and expression in the ovine lung. Molecular Therapy, 15(2), 348-354. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17235313

@article{4fc03b3256f54fe4a1dc71daf28053fa,

title = "Optimizing aerosol gene delivery and expression in the ovine lung",

abstract = "We have developed the sheep as a large animal model for optimizing cystic fibrosis gene therapy protocols. We administered aerosolized gene transfer agents (GTAs) to the ovine lung in order to test the delivery, efficacy, and safety of GTAs using a clinically relevant nebulizer. A preliminary study demonstrated GTA distribution and reporter gene expression throughout the lung after aerosol administration of plasmid DNA (pDNA):GL67 and pDNA:PEI complexes. A more comprehensive study examined the dose-response relationship for pDNA:PEI and assessed the influence of adjunct therapeutic agents. We found that the sheep model can differentiate between doses of GTA and that the anticholinergic, glycopyrrolate, enhanced transgene expression. Dose-related toxicity of GTA was reduced by aerosol administration compared to direct instillation. This large animal model will allow us to move toward clinical studies with greater confidence.",

keywords = "Animals Chloramphenicol O-Acetyltransferase/genetics/metabolism Female Gene Expression Gene Transfer Techniques/adverse effects/*instrumentation Genes, Reporter/genetics Genetic Vectors/*genetics Lung/*metabolism Lung Diseases/etiology/pathology Male *Nebulizers and Vaporizers Recombinant Fusion Proteins/genetics/metabolism Sheep",

author = "G. McLachlan and A. Baker and P. Tennant and C. Gordon and C. Vrettou and L. Renwick and R. Blundell and Cheng, {S. H.} and Scheule, {R. K.} and L. Davies and H. Painter and Coles, {R. L.} and Lawton, {A. E.} and C. Marriott and Gill, {D. R.} and Hyde, {S. C.} and U. Griesenbach and Alton, {E. W.} and Boyd, {A. C.} and Porteous, {D. J.} and Collie, {D. D.}",

note = "Feb Optimizing aerosol gene delivery and expression in the ovine lung Journal Article Research Support, Non-U.S. Gov't United States the journal of the American Society of Gene Therapy eng",

year = "2007",

language = "English",

volume = "15",

pages = "348--354",

journal = "Molecular Therapy",

issn = "1525-0016",

publisher = "Cell Press",

number = "2",

}

McLachlan, G, Baker, A, Tennant, P, Gordon, C, Vrettou, C, Renwick, L, Blundell, R, Cheng, SH, Scheule, RK, Davies, L, Painter, H, Coles, RL, Lawton, AE, Marriott, C, Gill, DR, Hyde, SC, Griesenbach, U, Alton, EW, Boyd, AC, Porteous, DJ & Collie, DD 2007, 'Optimizing aerosol gene delivery and expression in the ovine lung', Molecular Therapy, vol. 15, no. 2, pp. 348-354. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17235313>

TY - JOUR

T1 - Optimizing aerosol gene delivery and expression in the ovine lung

AU - McLachlan, G.

AU - Baker, A.

AU - Tennant, P.

AU - Gordon, C.

AU - Vrettou, C.

AU - Renwick, L.

AU - Blundell, R.

AU - Cheng, S. H.

AU - Scheule, R. K.

AU - Davies, L.

AU - Painter, H.

AU - Coles, R. L.

AU - Lawton, A. E.

AU - Marriott, C.

AU - Gill, D. R.

AU - Hyde, S. C.

AU - Griesenbach, U.

AU - Alton, E. W.

AU - Boyd, A. C.

AU - Porteous, D. J.

AU - Collie, D. D.

N1 - Feb Optimizing aerosol gene delivery and expression in the ovine lung Journal Article Research Support, Non-U.S. Gov't United States the journal of the American Society of Gene Therapy eng

PY - 2007

Y1 - 2007

N2 - We have developed the sheep as a large animal model for optimizing cystic fibrosis gene therapy protocols. We administered aerosolized gene transfer agents (GTAs) to the ovine lung in order to test the delivery, efficacy, and safety of GTAs using a clinically relevant nebulizer. A preliminary study demonstrated GTA distribution and reporter gene expression throughout the lung after aerosol administration of plasmid DNA (pDNA):GL67 and pDNA:PEI complexes. A more comprehensive study examined the dose-response relationship for pDNA:PEI and assessed the influence of adjunct therapeutic agents. We found that the sheep model can differentiate between doses of GTA and that the anticholinergic, glycopyrrolate, enhanced transgene expression. Dose-related toxicity of GTA was reduced by aerosol administration compared to direct instillation. This large animal model will allow us to move toward clinical studies with greater confidence.

AB - We have developed the sheep as a large animal model for optimizing cystic fibrosis gene therapy protocols. We administered aerosolized gene transfer agents (GTAs) to the ovine lung in order to test the delivery, efficacy, and safety of GTAs using a clinically relevant nebulizer. A preliminary study demonstrated GTA distribution and reporter gene expression throughout the lung after aerosol administration of plasmid DNA (pDNA):GL67 and pDNA:PEI complexes. A more comprehensive study examined the dose-response relationship for pDNA:PEI and assessed the influence of adjunct therapeutic agents. We found that the sheep model can differentiate between doses of GTA and that the anticholinergic, glycopyrrolate, enhanced transgene expression. Dose-related toxicity of GTA was reduced by aerosol administration compared to direct instillation. This large animal model will allow us to move toward clinical studies with greater confidence.

KW - Animals Chloramphenicol O-Acetyltransferase/genetics/metabolism Female Gene Expression Gene Transfer Techniques/adverse effects/instrumentation Genes, Reporter/genetics Genetic Vectors/genetics Lung/metabolism Lung Diseases/etiology/pathology Male Nebuliz

M3 - Article

SN - 1525-0016

VL - 15

SP - 348

EP - 354

JO - Molecular Therapy

JF - Molecular Therapy

IS - 2

ER -

Optimizing aerosol gene delivery and expression in the ovine lung

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Keywords / Materials (for Non-textual outputs)

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Optimising delivery and analysis of gene transfer in the sheep lung

Cite this