Enhancement of in vivo adenovirus-mediated gene transfer and expression by prior depletion of tissue macrophages in the target organ.
| Publication Type | Academic Article |
| Authors | Wolff G, Worgall S, van Rooijen N, Song W, Harvey B, Crystal R |
| Journal | J Virol |
| Volume | 71 |
| Issue | 1 |
| Pagination | 624-9 |
| Date Published | 01/01/1997 |
| ISSN | 0022-538X |
| Keywords | Adenoviruses, Human, Gene Transfer Techniques, Genetic Vectors, Kupffer Cells, Liver |
| Abstract | Based on the hypothesis that tissue macrophages present an obstacle for adenovirus (Ad) vector-mediated gene transfer to internal organs, this study evaluated the consequences of transient depletion of Kupffer cells on subsequent transfer of the Ad vector genome and Ad vector-directed gene expression in the livers of experimental animals. Depletion of Kupffer cells in mice by intravenous administration of multilamellar liposomes containing dichloromethylene-bisphosphonate permitted subsequent intravenous administration of an Ad vector to provide a higher input of recombinant adenoviral DNA to the liver, an absolute increase in transgene expression, and a delayed clearance of the vector DNA and transgene expression. These observations suggest that the tissue macrophages pose a significant hurdle to Ad vector-mediated gene transfer and that strategies to transiently suppress macrophage defenses might be useful in enhancing the efficiency of this in vivo gene transfer system. |
| DOI | 10.1128/JVI.71.1.624-629.1997 |
| PubMed ID | 8985392 |
| PubMed Central ID | PMC191093 |