Changing viral tropism using immunoliposomes alters the stability of gene expression: implications for viral vector design.
Many strategies for redirecting the tropism of murine Moloney leukemia virus (MMLV) have been described. Preformed virion-liposome complexes, termed virosomes, have been reported to be relatively stable. Virosomes mediate envelope-independent transduction that allows efficient superinfection of resistant cell lines; however, virosome-mediated transduction behaves in a non-target-specific manner. We developed a novel method using antibodies to direct MMLV to vascular endothelium. We have given the term immunovirosomes to the complexes formed between viruses, liposomes, and antibodies. These immunovirosomes improve the transduction efficiency of the viruses and alter their tropism. We have shown improved transduction when immunovirosomes were targeted at the endocytic receptors CD71 and CD62E/P and rather less good delivery when targeted at CD106. The enhancement of the transduction efficiency was transient, however, suggesting that rerouting the entry pathway of viruses alters the expression properties of the viruses.
Tan
Peng H
PH
Department of Immunology, Division of Medicine, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, UK. p.tan@imperial.ac.uk
Xue
Shao-An
SA
Wei
Bin
B
Holler
Angelika
A
Voss
Ralf-Holger
RH
George
Andrew J T
AJ
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D019040:E-Selectin / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005814:Genes, Viral; D006801:Humans; D006825:Hybridomas; D008081:Liposomes; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000378:metabolism; D011990:Receptors, Transferrin / Q000276:immunology / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic; D018523:Tropism; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D022701:Virosomes / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C068126:CD71 antigen; D019040:E-Selectin; D008081:Liposomes; D011990:Receptors, Transferrin; D019010:Vascular Cell Adhesion Molecule-1; D022701:Virosomes