Site-Specific Gene Delivery in vivo through Engineered Sendai Viral Envelopes

Inspite of several stimulating developments in gene therapy, the formulation of a targeted gene delivery "vector" is still far from ideal. We have demonstrated the potential of reconstituted Sendai viral envelopes containing only the fusion glycoprotein (F-virosomes) in targeted delivery o...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1998-09, Vol.95 (20), p.11886-11890
Main Authors: Ramani, Komal, Hassan, Quamarul, Venkaiah, Betapudi, Hasnain, Seyed E., Sarkar, Debi P.
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Cells
Chloramphenicol O-Acetyltransferase - genetics
Chromosomes - genetics
DNA
DNA - administration & dosage
DNA - genetics
Female
Gene Expression
Genes
Genes, Reporter
Genetic Engineering
Genetic Vectors
Genetics
Hepatocytes
Liver
Liver - cytology
Liver - enzymology
Liver cells
Luciferases - genetics
Membrane Fusion
Mice
Mice, Inbred BALB C
Plasmids
Polymerase chain reaction
Respirovirus - genetics
Reverse transcriptase polymerase chain reaction
Viruses
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Summary:Inspite of several stimulating developments in gene therapy, the formulation of a targeted gene delivery "vector" is still far from ideal. We have demonstrated the potential of reconstituted Sendai viral envelopes containing only the fusion glycoprotein (F-virosomes) in targeted delivery of reporter genes to liver cells of BALB/c mouse in vivo. The membrane fusion-mediated high efficiency of gene transfer to liver cells was ascertained following a critical evaluation of the level of the DNA, mRNA, and relevant proteins. Furthermore, the involvement of viral glycoprotein both as a unique natural ligand and as a membrane fusogen could lead to preferential transfection of parenchymal cell types of liver. The integration of transgenes in the mouse chromosomal DNA and its stable expression up to 4 mo after single i.v. administration of this gene carrier has bolstered its efficiency and novelty. Moreover, the F-virosomes did not elicit significant humoral immune response against the fusion protein in the injected animal. The findings reported here open up the possibility for considering "F-virosomes" as a promising "vehicle" for sitespecific DNA delivery in gene therapy.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.95.20.11886