Semliki Forest virus is an efficient and selective vector for gene delivery in infarcted rat heart.
Gene therapy is emerging as a realistic addition to the therapeutic arsenal in heart failure, but the search for suitable vectors for cardiac transfection is still ongoing. In this study, we explore the applicability of recombinant Semliki Forest virus (SFV) in heart failure. SFV was intracoronarily delivered 2 weeks after induction of myocardial infarction in the rat model for heart failure. Duration of SFV expression was determined, and tissue distribution was studied by histochemical, biochemical, and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses. Expression of SFV-mediated transfection in the heart reached its maximum after 48-72 h and subsided within a week. Intracoronary administration of SFV efficiently transfected the non-infarcted cardiac wall, resulting in high levels of beta-galactosidase (beta-gal) activity (1337 +/- 537 IU/mg) and lacZ RNA in the hearts of all rats, whereas brain, kidney, liver, lung, spleen, and testis were lacZ negative. In conclusion, intracoronarily delivered SFV has a favourable distribution pattern, showing expression of the transgene restricted to the heart.
Loot
Annemarieke E
AE
Department of Clinical Pharmacology, Molecular Virology Section, University of Groningen, The Netherlands. a.e.loot@med.rug.nl
Henning
Robert H
RH
Deelman
Leo E
LE
Tio
René A
RA
Schoen
Pieter
P
Wilschut
Jan C
JC
van Gilst
Wiek H
WH
Roks
Anton J M
AJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007249:Inflammation; D007763:Lac Operon; D008264:Macrophages / Q000378:metabolism; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012672:Semliki forest virus / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection; D019076:Transgenes; D001616:beta-Galactosidase / Q000378:metabolism
D012333:RNA, Messenger; D012313:RNA; D001616:beta-Galactosidase