Adenovirus-mediated transfer of the CFTR gene to lung of nonhuman primates: toxicity study

Human Gene Therapy
R H SimonJ M Wilson

Abstract

In preparation for human trials of gene therapy for cystic fibrosis (CF), we performed a preclinical study of gene transfer into the lungs of baboons. Recombinant adenovirus vectors containing expression cassettes for human cystic fibrosis transmembrane conductance regulator (CFTR) and Escherichia coli beta-galactosidase (lacZ) were instilled through a bronchoscope into limited regions of lung in 14 baboons. A detailed accounting of the extent, distribution, and duration of gene expression is contained in a companion article (Engelhardt et al., 1993b). In this article, we report the results of toxicity studies in which clinical laboratory tests, chest radiographs, and necropsy studies were used to detect adverse effects. The only adverse effect noted was a mononuclear cell inflammatory response within the alveolar compartment of animals receiving doses of virus that were required to induce detectable gene expression. Minimal inflammation was seen at 10(7) and 10(8) pfu/ml, but at 10(9) and more prominently at 10(10) pfu/ml, a perivascular lymphocytic and histiocytic infiltrate was seen. The intensity of inflammation increased between 4 and 21 days. At its greatest intensity, there was diffuse alveolar wall damage with intra-alv...Continue Reading

References

Dec 1, 1973·The Journal of Infectious Diseases·G G Jackson, R L Muldoon
Jan 1, 1983·Current Topics in Pathology. Ergebnisse Der Pathologie·H E Schaefer

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Citations

Jan 1, 1995·Journal of Inherited Metabolic Disease·A E Smith
Dec 1, 1994·Current Opinion in Biotechnology·B C Trapnell, M Gorziglia
Dec 1, 1994·Current Opinion in Biotechnology·R C Boucher
Dec 31, 2003·International Journal of Pharmaceutics·Masaki TokunagaToshihisa Yotsuyanagi
Jan 1, 1997·Journal of Neuroscience Methods·M G Kaplitt, H Makimura
Feb 22, 2001·Veterinary Immunology and Immunopathology·D F Morrison, M P Murtaugh
Feb 16, 2000·Journal of Neuroimmunology·K KajiwaraK J Wood
Nov 24, 2001·Advanced Drug Delivery Reviews·G Borchard
Jun 6, 2000·Advanced Drug Delivery Reviews·E Alton, D Geddes
Jun 6, 2000·Advanced Drug Delivery Reviews·X XingM Hung
Feb 5, 2000·Experimental Hematology·N D TranE D Zanjani
Feb 16, 1999·International Journal of Radiation Oncology, Biology, Physics·M W EpperlyJ S Greenberger
Oct 25, 2000·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·S D CassiviS H Keshavjee
Jul 20, 2002·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·John Nemunaitis, Casey Cunningham
Jan 20, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Terence R FlotteJim Hu
May 10, 1994·Proceedings of the National Academy of Sciences of the United States of America·Y YangJ M Wilson
Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·H SakamotoM Terada
Jun 11, 1996·Proceedings of the National Academy of Sciences of the United States of America·S KochanekC T Caskey
Nov 22, 2002·DNA and Cell Biology·Frank MartiniukWilliam N Rom
Feb 1, 1995·Human Gene Therapy·W W ZhangJ A Roth

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