Safety of airway gene transfer with Ad2/CFTR2

Aerosol administration in the nonhuman primate

Ruth J McDonald, Micheal J. Lukason, Otto G. Raabe, Don R. Canfield, Elizabeth A. Burr, Johanne M. Kaplan, Samuel C. Wadsworth, Judith A. St. George

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

In this study, the safety and efficacy of aerosol delivery to non-human primates of an adenoviral vector encoding the cystic fibrosis transmembrane conductance regulator protein (CFTR) were evaluated. The technique of concurrent flow spirometry was used to determine the deposited dose of Ad2/CFTR-2, which ranged from 3 to 8 x 1010 I.U. Transgene DNA was detected by the polymerase chain reaction (PCR) in lung tissue from all treated animals, and human CFTR mRNA was detected on days 3, 7, and 21 post-exposure. The treatment was well tolerated, with no evidence of respiratory distress. Histologic changes in the lungs from Ad2/CFTR-2-treated animals were mild and, overall, indistinguishable from animals exposed to aerosolized vehicle. One vector-treated animal demonstrated an increase in lavage lymphocyte numbers 3 days after treatment and another had an abnormal chest radiograph 14 days after treatment. A third vector-treated animal had histologic evidence of a bronchointerstitial pneumonia 7 days after aerosol treatment that resolved by day 21. This study demonstrated that Ad2/CFTR-2 can effectively be delivered to the lungs of nonhuman primates and result in minimal adverse effects.

Original languageEnglish (US)
Pages (from-to)411-422
Number of pages12
JournalHuman Gene Therapy
Volume8
Issue number4
StatePublished - Mar 1 1997

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Cystic Fibrosis Transmembrane Conductance Regulator
Aerosols
Primates
Safety
Genes
Proteins
Lung
Therapeutic Irrigation
Spirometry
Lymphocyte Count
Therapeutics
Transgenes
Pneumonia
Thorax
Polymerase Chain Reaction
Messenger RNA
DNA

ASJC Scopus subject areas

  • Genetics

Cite this

McDonald, R. J., Lukason, M. J., Raabe, O. G., Canfield, D. R., Burr, E. A., Kaplan, J. M., ... St. George, J. A. (1997). Safety of airway gene transfer with Ad2/CFTR2: Aerosol administration in the nonhuman primate. Human Gene Therapy, 8(4), 411-422.

Safety of airway gene transfer with Ad2/CFTR2 : Aerosol administration in the nonhuman primate. / McDonald, Ruth J; Lukason, Micheal J.; Raabe, Otto G.; Canfield, Don R.; Burr, Elizabeth A.; Kaplan, Johanne M.; Wadsworth, Samuel C.; St. George, Judith A.

In: Human Gene Therapy, Vol. 8, No. 4, 01.03.1997, p. 411-422.

Research output: Contribution to journalArticle

McDonald, RJ, Lukason, MJ, Raabe, OG, Canfield, DR, Burr, EA, Kaplan, JM, Wadsworth, SC & St. George, JA 1997, 'Safety of airway gene transfer with Ad2/CFTR2: Aerosol administration in the nonhuman primate', Human Gene Therapy, vol. 8, no. 4, pp. 411-422.
McDonald RJ, Lukason MJ, Raabe OG, Canfield DR, Burr EA, Kaplan JM et al. Safety of airway gene transfer with Ad2/CFTR2: Aerosol administration in the nonhuman primate. Human Gene Therapy. 1997 Mar 1;8(4):411-422.
McDonald, Ruth J ; Lukason, Micheal J. ; Raabe, Otto G. ; Canfield, Don R. ; Burr, Elizabeth A. ; Kaplan, Johanne M. ; Wadsworth, Samuel C. ; St. George, Judith A. / Safety of airway gene transfer with Ad2/CFTR2 : Aerosol administration in the nonhuman primate. In: Human Gene Therapy. 1997 ; Vol. 8, No. 4. pp. 411-422.
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