| | |  | | | | Record from Web of Science® | | | | | | |
| Immune responses to transgene-encoded proteins limit the stability of gene expression after injection of replication-defective adenovirus vectors |
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| Author(s): Tripathy SK, Black HB, Goldwasser E, Leiden JM |
| Source: NATURE MEDICINE Volume: 2 Issue: 5 Pages: 545-550 Published: MAY 1996 |
| Times Cited: 506 References: 30 |
| Abstract: The use of replication-defective adenoviruses (RDAd) for human gene therapy has been limited by host immune responses that result in transient recombinant gene expression in vivo. It remained unclear whether these immune responses were directed predominantly against viral proteins or, alternatively, against foreign transgene-encoded proteins. In this report, we have compared the stability of recombinant gene expression in adult immunocompetent mice following intramuscular (i.m.) injection with identical RDAd encoding self (murine) or foreign (human) erythropoietin. Our results demonstrate that immune responses directed against foreign transgene-encoded proteins are the major determinants of the stability of gene expression following i.m. injection of RDAd. Moreover, we demonstrate long-term recombinant gene expression in immunocompetent animals following a single i.m. injection of RDAd encoding a self protein. These findings are important for the design of future preclinical and clinical gene therapy trials. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV CHICAGO, DEPT MED, CHICAGO, IL 60637 USA
2. UNIV CHICAGO, DEPT BIOCHEM, CHICAGO, IL 60637 USA
3. UNIV CHICAGO, DEPT MOLEC BIOL, CHICAGO, IL 60637 USA
4. UNIV CHICAGO, DEPT PATHOL, CHICAGO, IL 60637 USA |
| Publisher: NATURE PUBLISHING CO, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental |
| IDS Number: UJ230 |
| ISSN: 1078-8956 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |