Readministration of helper-dependent adenovirus to mouse lung
- 26 January 2006
- journal article
- Published by Springer Nature in Gene Therapy
- Vol. 13 (9) , 773-780
- https://doi.org/10.1038/sj.gt.3302712
Abstract
Adenovirus vectors (Ad) are widely used in gene therapy studies, including those aimed at treating cystic fibrosis lung disease. Various approaches have been investigated to blunt the host immune response to Ad, including development of helper-dependent (HD) Ad. The host cytotoxic T-cell response to HD-Ad is generally lower than to earlier-generation Ad. However, antibodies are formed which could inhibit the efficacy of HD-Ad readministration. In this first study of HD-Ad readministration to the lung, we found that a second administration of HD-Ad to mice was possible with minimal loss of transgene expression. In contrast, when first-generation (FG) Ad was administered initially, followed by HD-Ad or FG-Ad, transgene expression was reduced. Significantly lower concentrations of antibodies against Ad were found in lung lavage fluid and serum from mice that received two doses of HD-Ad (when the initial HD-Ad lacked a transgene), compared to mice that received FG-Ad followed by HD-Ad. These data suggest that readministration of HD-Ad for lung gene therapy may be feasible.Keywords
This publication has 52 references indexed in Scilit:
- Vaccination with helper-dependent adenovirus enhances the generation of transgene-specific CTLGene Therapy, 2004
- Role of Viral Vectors and Virion Shells in Cellular Gene ExpressionMolecular Therapy, 2004
- Prevalence of Neutralizing Antibodies to Adenoviral Serotypes 5 and 35 in the Adult Populations of The Gambia, South Africa, and the United StatesClinical and Vaccine Immunology, 2004
- Recovery of Airway Cystic Fibrosis Transmembrane Conductance Regulator Function in Mice with Cystic Fibrosis After Single-Dose Lentivirus-Mediated Gene TransferHuman Gene Therapy, 2002
- Multiple Advantages of α-Fetoprotein as a Marker for in Vivo Gene TransferMolecular Therapy, 2000
- Use of helper-dependent adenoviral vectors of alternative serotypes permits repeat vector administrationGene Therapy, 1999
- Adenovirus-mediated gene transfer: influence of transgene, mouse strain and type of immune response on persistence of transgene expressionGene Therapy, 1997
- Characterization of Factors Involved in Modulating Persistence of Transgene Expression from Recombinant Adenovirus in the Mouse LungHuman Gene Therapy, 1997
- Immunological Memory and Protective Immunity: Understanding Their RelationScience, 1996
- Characteristics of a Human Cell Line Transformed by DNA from Human Adenovirus Type 5Journal of General Virology, 1977