Delivery of viral vectors to hepatic stellate cells in fibrotic livers using HVJ envelopes fused with targeted liposomes.
Hepatic stellate cells (HSC) are a major target for antifibrotic therapies in the liver and in particular gene delivery to these cells would be relevant. Previously, we demonstrated that mannose 6-phosphate human serum albumin (M6P-HSA) coupled liposomes accumulate in HSC in fibrotic livers. Here we prepared a M6P-HSA modified viral vector that allows the targeted delivery of plasmid DNA to HSC. Therefore, UV inactivated hemagglutinating virus of Japan (HVJ) containing plasmid DNA was fused with M6P-HSA liposomes to yield HVJ liposomes targeted to HSC. These new particles had a diameter of approximately 200 nm, as determined by electron microscopy. In a carbon tetrachloride mouse model of liver fibrosis, M6P-HSA-HVJ-liposomes associated with HSC. In conclusion, our results demonstrate that fusion of M6P-HSA liposomes with HVJ envelopes results in HVJ particles that accumulate in HSC, allowing for new possibilities to interfere with fibrosis in the liver.
Adrian
Joanna E
JE
Medical Biology section, Department of Pathology and Laboratory Medicine, University Medical Center Groningen (UMCG), University of Groningen. Hanzeplein 1, Groningen 9713 GZ, The Netherlands. j.e.adrian@med.umcg.rug.nl
Kamps
Jan A A M
JA
Poelstra
Klaas
K
Scherphof
Gerrit L
GL
Meijer
Dirk K F
DK
Kaneda
Yasufumi
Y
D000818:Animals; D045744:Cell Line, Tumor; D002642:Chick Embryo; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004591:Electrophoresis, Polyacrylamide Gel; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D007150:Immunohistochemistry; D008081:Liposomes; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008156:Luciferases / Q000235:genetics; D008360:Mannosephosphates / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D010957:Plasmids / Q000235:genetics; D029082:Sendai virus / Q000378:metabolism*; D012709:Serum Albumin / Q000737:chemistry; D014759:Viral Envelope Proteins / Q000737:chemistry*
D008081:Liposomes; D008360:Mannosephosphates; D012709:Serum Albumin; D014759:Viral Envelope Proteins; C027693:mannose-6-phosphate; D004247:DNA; D008156:Luciferases