(Strept)avidin-displaying lentiviruses as versatile tools for targeting and dual imaging of gene delivery.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9421525 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5462 (Electronic) Linking ISSN: 09697128 NLM ISO Abbreviation: Gene Ther Subsets: MEDLINE

Publication: London : Nature Publishing Group
Original Publication: Houndmills, Basingstoke, Hampshire, UK : Macmillan Press Ltd., c1994-

Avidin/*metabolism ; Gene Expression Profiling/*methods ; Genetic Vectors/*genetics ; Lentivirus/*genetics ; Streptavidin/*metabolism; Animals ; Baculoviridae/genetics ; Biotinylation ; Brain/metabolism ; Cell Line, Tumor ; Culture Media ; Enzyme-Linked Immunosorbent Assay ; ErbB Receptors/metabolism ; Ferritins/genetics ; Ferritins/metabolism ; Gene Transfer Techniques ; Genes, Reporter ; Green Fluorescent Proteins/metabolism ; Humans ; Ligands ; Magnetic Resonance Imaging/methods ; Male ; Membrane Cofactor Protein/metabolism ; Membrane Glycoproteins/metabolism ; Plasmids ; Rats ; Receptors, Transferrin/metabolism ; Recombinant Fusion Proteins/metabolism ; Stereotaxic Techniques ; Tissue Distribution ; Tomography, Emission-Computed, Single-Photon/methods ; Transduction, Genetic/methods ; Transduction, Genetic/standards ; Transgenes ; Viral Envelope Proteins/metabolism ; Viral Tropism/genetics

Lentiviruses have shown great promise for human gene therapy. However, no optimal strategies are yet available for noninvasive imaging of virus biodistribution and subsequent transduction in vivo. We have developed a dual-imaging strategy based on avidin-biotin system allowing easy exchange of the surface ligand on HIV-derived lentivirus envelope. This was achieved by displaying avidin or streptavidin fused to the transmembrane anchor of vesicular stomatitis virus G protein on gp64-pseudotyped envelopes. Avidin and streptavidin were efficiently incorporated on virus particles, which consequently showed binding to biotin in ELISA. These vectors, conjugated to biotinylated radionuclides and engineered to express a ferritin transgene, enabled for the first-time dual imaging of virus biodistribution and transduction pattern by single-photon emission computed tomography and magnetic resonance imaging after stereotactic injection into rat brain. In addition, vector retargeting to cancer cells overexpressing CD46, epidermal growth factor and transferrin receptors using biotinylated ligands and antibodies was demonstrated in vitro. In conclusion, we have generated novel lentivirus vectors for noninvasive imaging and targeting of lentivirus-mediated gene delivery. This study suggests that these novel vectors could be applicable for the treatment of central nervous system disorders and cancer.

0 (CD46 protein, human)
0 (Culture Media)
0 (G protein, vesicular stomatitis virus)
0 (Ligands)
0 (Membrane Cofactor Protein)
0 (Membrane Glycoproteins)
0 (Receptors, Transferrin)
0 (Recombinant Fusion Proteins)
0 (Viral Envelope Proteins)
1405-69-2 (Avidin)
147336-22-9 (Green Fluorescent Proteins)
9007-73-2 (Ferritins)
9013-20-1 (Streptavidin)
EC 2.7.10.1 (ErbB Receptors)

Date Created: 20090515 Date Completed: 20100730 Latest Revision: 20181201

20240829

10.1038/gt.2009.47

19440224