Retroviral vectors preloaded with a viral receptor-ligand bridge protein are targeted to specific cell types.
Successful targeting methods represent a major hurdle to the use of retroviral vectors in cell-specific gene-delivery applications. We recently described an approach for retroviral targeting with a retroviral receptor-ligand bridge protein that was bound to the cognate cell-surface ligand receptors before viral challenge. We now report a significant improvement made to this viral targeting method by using a related bridge protein, designated TVB-EGF, comprised of the extracellular domain of the TVB receptor for subgroup B avian leukosis virus fused to epidermal growth factor (EGF). The most important activity of TVB-EGF was that it allowed specific viral entry when preloaded onto virions. Furthermore, virions preloaded with TVB-EGF were thermostable and could be produced directly from virus- packaging cells. These data suggest an approach for targeting retroviral vectors to specific cell types by using virions preloaded with a retroviral receptor-ligand bridge protein and indicate that these types of bridge proteins may be useful reagents for studying the normal mechanism of retroviral entry.
Boerger
A L
AL
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston MA 02115, USA.
Snitkovsky
S
S
Young
J A
JA
D001354:Avian Leukosis Virus; D030161:Avian Proteins; D002460:Cell Line; D003432:Cross-Linking Reagents / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000235:genetics* / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005434:Flow Cytometry; D005822:Genetic Vectors; D006801:Humans; D008024:Ligands; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012190:Retroviridae; D014162:Transfection / Q000379:methods*; D014771:Virion / Q000472:pathogenicity
D030161:Avian Proteins; D003432:Cross-Linking Reagents; D008024:Ligands; D018124:Receptors, Tumor Necrosis Factor; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C088745:Tva receptor; D004815:Epidermal Growth Factor; D066246:ErbB Receptors