We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
<em>Ex Vivo</em> and <em>In Vivo</em> Gene Transfer to The Skin Using Replication-Deficient Recombinant Adenovirus Vectors.
- Authors
Setoguchi, Yasuhiro; Jaffe, H. Ari; Danel, Claire; Crystal, Ronald G.
- Abstract
The skin has the potential for a variety of gene therapy applications. In addition to local delivery, it is the largest organ of the body, and highly vascular, and thus is an ideal site for systemic delivery of gene products. To evaluate the potential for adenovirus-mediated skin gene transfer, the replication-deficient recombinant adenovirus vectors Ad.RSV βgal (coding for <em>Escherichia coli</em> β-galactosidase) and Adα1AT (coding for human α1-antitrypsin) were used in both <em>ex vivo</em> and <em>in vivo</em> approaches. Following <em>in vitro</em> infection with Ad.RSV βgal, murine keratinocytes expressed β-galactosidase. Parallel <em>in vitro</em> studies with Adα1AT documented <em>de novo</em> synthesis and secretion of human α1AT as shown by [35S]methionine labeling and immunoprecipitation. Quantification of human α1AT in the culture supernatants demonstrated 0.1 -0.3 μg human α1AT secreted/ml-24 h. Evaluation of the serum of mice receiving transplants (10 5 cells/ mouse) of Adα1AT-infected syngeneic keratinocytes demonstrated human α1AT for at least 14 d with maximum levels of 41 ng/ml. To demonstrate the feasibility of direct adenovirus-mediated <em>in vivo</em> transfer of genes to the skin, Ad.RSV βgal or Adα1AT were administered subcutaneously to mice. Histologic evaluation after 4 d demonstrated expression of β-galactosidase in various types of skin cells. Quantification of human α1AT in serum of animals infected subcutaneously with Adα1AT showed levels of 53 ng/ml at day 4, with human α1AT detectable for at least 14 d. These observations support the feasibility of <em>ex vivo</em> and <em>in vivo</em> gene transfer to the skin mediated by replication-deficient adenovirus vectors.
- Subjects
GENE therapy; GENETIC engineering; KERATINOCYTES; IMMUNOLOGY; MICE; ESCHERICHIA coli
- Publication
Journal of Investigative Dermatology, 1994, Vol 102, Issue 4, p415
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1111/1523-1747.ep12372181