Open AccessEx vivo intracoronary gene transfer of adeno‐associated virus 2 leads to superior transduction over serotypes 8 and 9 in rat heart transplants
Author(s) -
Raissadati Alireza,
Jokinen Janne J.,
Syrjälä Simo O.,
Keränen Mikko A. I.,
Krebs Rainer,
Tuuminen Raimo,
Arnaudova Ralica,
Rouvinen Eeva,
Anisimov Andrey,
Soronen Jarkko,
Pajusola Katri,
Alitalo Kari,
Nykänen Antti I.,
Lemström Karl
Publication year - 2013
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/tri.12182
Subject(s) - ex vivo , adeno associated virus , syngenic , in vivo , transduction (biophysics) , bioluminescence imaging , medicine , luciferase , genetic enhancement , gene delivery , reporter gene , transplantation , pathology , biology , immunology , gene expression , microbiology and biotechnology , gene , transfection , vector (molecular biology) , biochemistry , recombinant dna
Summary Heart transplant gene therapy requires vectors with long‐lasting gene expression, high cardiotropism, and minimal pathological effects. Here, we examined transduction properties of ex vivo intracoronary delivery of adeno‐associated virus ( AAV ) serotype 2, 8, and 9 in rat syngenic and allogenic heart transplants. Adult Dark Agouti ( DA ) rat hearts were intracoronarily perfused ex vivo with AAV 2, AAV 8, or AAV 9 encoding firefly luciferase and transplanted heterotopically into the abdomen of syngenic DA or allogenic Wistar–Furth ( WF ) recipients. Serial in vivo bioluminescent imaging of syngraft and allograft recipients was performed for 6 months and 4 weeks, respectively. Grafts were removed for PCR ‐, RT ‐ PCR , and luminometer analysis. In vivo bioluminescent imaging of recipients showed that AAV 9 induced a prominent and stable luciferase activity in the abdomen, when compared with AAV 2 and AAV 8. However, ex vivo analyses revealed that intracoronary perfusion with AAV 2 resulted in the highest heart transplant transduction levels in syngrafts and allografts. Ex vivo intracoronary delivery of AAV 2 resulted in efficient transgene expression in heart transplants, whereas intracoronary AAV 9 escapes into adjacent tissues. In terms of cardiac transduction, these results suggest AAV 2 as a potential vector for gene therapy in preclinical heart transplants studies, and highlight the importance of delivery route in gene transfer studies.