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 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 site-specific DNA delivery in gene therapy.
Ramani
K
K
Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, New Delhi-110021, India.
Hassan
Q
Q
Venkaiah
B
B
Hasnain
S E
SE
Sarkar
D P
DP
D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D002875:Chromosomes / Q000235:genetics; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D005818:Genetic Engineering; D005822:Genetic Vectors; D008099:Liver / Q000166:cytology / Q000201:enzymology; D008156:Luciferases / Q000235:genetics; D008561:Membrane Fusion; D051379:Mice; D008807:Mice, Inbred BALB C; D018108:Respirovirus / Q000235:genetics*
D004247:DNA; D008156:Luciferases; D015500:Chloramphenicol O-Acetyltransferase