Direct In Vivo Gene Transfer and Expression in Malignant Cells Using Adenovirus Vectors

Steven L. Brody, H. Ari Jaffe, Sung Koo Han, Robert P. Wersto, Ronald Crystal

Research output: Contribution to journalArticle

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Abstract

To evaluate the ability of replication-deficient, recombinant adenovirus vectors to transfer genes to human tumor cells in vivo, adenovirus vectors containing the Escherichia coli lacZ (Ad.RSVβgal) gene (coding for β-galactosidase; used as a cell marker for gene transfer) or the human α1-antitrypsin (Ad-α1AT) cDNA (used as an example of a secreted protein) were administered intraperitoneally to nude mice with human malignant mesothelioma cell (H-MESO-1) malignant ascites. Preliminary in vitro studies showed that both vectors effectively transferred genes to H-MESO-1 cells. Tumor cells recovered from ascites of animals intraperitoneally administered a control adenovirus revealed no evidence of β-galactosidase (β-gal) activity 3 or 14 days later. In contrast, β-gal activity was detected at the same time points in tumor cells from animals receiving intraperitoneal Ad.RSVβgal. Flow cytometric quantification of β-gal activity in recovered cells showed <3% β-gal-positive cells in animals administered control virus, but in animals administered intraperitoneal Ad.RSVβ gal there was a mean of 71 ± 18% positive cells at 3 days and 56 ± 27% at 14 days. Human α1AT was not detected by enzyme-linked immunosorbent assay (ELISA) in ascites of animals receiving a control virus; however, in ascites of animals administered Ad-α1AT, 21,000 ± 3,800 ng/ml of human α1AT was detected at 3 days and 4,900 ± 1,700 ng/ml at 14 days. These data demonstrate that replication-deficient recombinant adenovirus vectors can be used to transfer genes to malignant cells in vivo and suggest a new strategy for genetic modification for antitumor therapy.

Original languageEnglish
Pages (from-to)437-447
Number of pages11
JournalHuman Gene Therapy
Volume5
Issue number4
DOIs
Publication statusPublished - 1 Apr 1994
Externally publishedYes

Fingerprint

Adenoviridae
Gene Expression
Ascites
Galactosidases
Genes
Viruses
Neoplasms
Nude Mice
Complementary DNA
Enzyme-Linked Immunosorbent Assay
Escherichia coli

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Direct In Vivo Gene Transfer and Expression in Malignant Cells Using Adenovirus Vectors. / Brody, Steven L.; Jaffe, H. Ari; Han, Sung Koo; Wersto, Robert P.; Crystal, Ronald.

In: Human Gene Therapy, Vol. 5, No. 4, 01.04.1994, p. 437-447.

Research output: Contribution to journalArticle

Brody, Steven L. ; Jaffe, H. Ari ; Han, Sung Koo ; Wersto, Robert P. ; Crystal, Ronald. / Direct In Vivo Gene Transfer and Expression in Malignant Cells Using Adenovirus Vectors. In: Human Gene Therapy. 1994 ; Vol. 5, No. 4. pp. 437-447.
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