Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 14 August 1987:
Vol. 237. no. 4816, pp. 762 - 764
DOI: 10.1126/science.3497452
Prev | Table of Contents | Next

Articles

Science, Vol 237, Issue 4816, 762-764
Copyright © 1987 by American Association for the Advancement of Science

articles

Clonal gene therapy: transplanted mouse fibroblast clones express human alpha 1-antitrypsin gene in vivo

RI Garver Jr, A Chytil, M Courtney, and RG Crystal

A retroviral vector was used to insert human alpha 1-antitrypsin (alpha 1AT) complementary DNA into the genome of mouse fibroblasts to create a clonal population of mouse fibroblasts secreting human alpha 1AT. After demonstrating that this clone of fibroblasts produced alpha 1AT after more than 100 population doublings in the absence of selection pressure, the clone was transplanted into the peritoneal cavities of nude mice. When the animals were evaluated 4 weeks later, human alpha 1AT was detected in both sera and the epithelial surface of the lungs. The transplanted clone of fibroblasts could be recovered from the peritoneal cavities of those mice and demonstrated to still be producing human alpha 1AT. Thus, even after removal of selective pressure, a single clone of retroviral vector-infected cells that expressed an exogenous gene in vitro, continued to do so in vivo, and when recovered, continued to produce the product of the exogenous gene.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Sustained Expression of {alpha}1-Antitrypsin after Transplantation of Manipulated Hematopoietic Stem Cells.
A. A. Wilson, L. W. Kwok, A.-H. Hovav, S. J. Ohle, F. F. Little, A. Fine, and D. N. Kotton (2008)
Am. J. Respir. Cell Mol. Biol. 39, 133-141
   Abstract »    Full Text »    PDF »
American Thoracic Society/European Respiratory Society Statement: Standards for the Diagnosis and Management of Individuals with Alpha-1 Antitrypsin Deficiency.
(2003)
Am. J. Respir. Crit. Care Med. 168, 818-900
   Full Text »    PDF »
sFlt-1 Gene-transfected Fibroblasts: A Wound-specific Gene Therapy Inhibits Local Cancer Recurrence.
W. Yang, S. Arii, A. Mori, K. Furumoto, T. Nakao, N. Isobe, T. Murata, H. Onodera, and M. Imamura (2001)
Cancer Res. 61, 7840-7845
   Abstract »    Full Text »    PDF »
Research Opportunities and Advances in Lung Disease.
R. G. Crystal (2001)
JAMA 285, 612-618
   Abstract »    Full Text »    PDF »
Gene Therapy for Lung Disease: Hype or Hope?.
S. M. Albelda, R. Wiewrodt, and J. B. Zuckerman (2000)
Ann Intern Med 132, 649-660
   Abstract »    Full Text »    PDF »
Sustained secretion of human alpha-1-antitrypsin from murine muscle transduced with adeno-associated virus vectors.
S. Song, M. Morgan, T. Ellis, A. Poirier, K. Chesnut, J. Wang, M. Brantly, N. Muzyczka, B. J. Byrne, M. Atkinson, et al. (1998)
PNAS 95, 14384-14388
   Abstract »    Full Text »    PDF »
Pulmonary Cell Biology.
R. J. MASON and R. G. CRYSTAL (1998)
Am. J. Respir. Crit. Care Med. 157, S72-S81
   Full Text »    PDF »
Gene Therapy for Cardiovascular Disease.
E. G. Nabel (1995)
Circulation 91, 541-548
   Full Text »
Dermal fibroblasts convert to a myogenic lineage in mdx mouse muscle.
A. Gibson, J Karasinski, J Relvas, J Moss, T. Sherratt, P. Strong, and D. Watt (1995)
J. Cell Sci. 108, 207-214
   Abstract »    PDF »
Systemic delivery of human growth hormone by injection of genetically engineered myoblasts.
J Dhawan, L. Pan, G. Pavlath, M. Travis, A. Lanctot, and H. Blau (1991)
Science 254, 1509-1512
   Abstract »    PDF »
Variability of Pulmonary Function in Alpha-1-Antitrypsin Deficiency: Clinical Correlates.
E. K. Silverman, J. A. Pierce, M. A. Province, D. C. Rao, and E. J. Campbell (1989)
Ann Intern Med 111, 982-991
   Abstract »    PDF »
High-level recombinant gene expression in rabbit endothelial cells transduced by retroviral vectors.
J. Zwiebel, S. Freeman, P. Kantoff, K Cornetta, U. Ryan, and W. Anderson (1989)
Science 243, 220-222
   Abstract »    PDF »
Grafting genetically modified cells to the damaged brain: restorative effects of NGF expression.
M. Rosenberg, T Friedmann, R. Robertson, M Tuszynski, J. Wolff, X. Breakefield, and F. Gage (1988)
Science 242, 1575-1578
   Abstract »    PDF »
Antitrypsin and Emphysema: Perspective and Prospects.
J. A. Pierce (1988)
JAMA 259, 2890-2895
   Abstract »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)