title: A nanobiohybrid complex of recombinant baculovirus and Tat/DNA nanoparticles for delivery of Ang-1 transgene in myocardial infarction therapy.
abstract: The study aims to design a new gene delivery method utilizing the complementary strengths of baculovirus, such as relatively high transduction efficiency and easy scale-up, and non-viral nanodelivery systems, such as low immunogenicity. This formulation was developed by generating a self assembled binary complex of negatively charged baculovirus (Bac) and positively charged endosomolytic histidine rich Tat peptide/DNA nanoparticles (NP). The synergistic effect of this hybrid (Bac-NP) system to induce myocardial angiogenesis in acute myocardial infarction (AMI) model has been explored in this study, using Angiopoietin-1 (Ang-1) as the transgene carried by both vector components. Under optimal transduction conditions, Bac-NP(Ang1) showed 1.75 times higher and sustained Ang-1 expression in cardiomyocytes than Bac(Ang1), with significantly high angiogenic potential as confirmed by functional assays. For in vivo analysis, we intramyocardially delivered Bac-NP(Ang1) to AMI rat model. 3 weeks post AMI, data showed increase in capillary density (p < 0.01) and reduction in infarct sizes (p < 0.05) in Bac-NP(Ang1) compared to Bac(Ang1), NP(Ang1) and control groups due to enhanced myocardial Ang-1 expression at peri-infarct regions (1.65 times higher than Bac(Ang1)). Furthermore, the Bac-NP(Ang1) group showed significantly higher cardiac performance in echocardiography than Bac(Ang1) (44.2 ± 4.77% vs 37.46 ± 5.2%, p < 0.01), NP(Ang1) and the control group (32.26 ± 2.49% and 31.58 ± 2.26%). Collectively, this data demonstrates hybrid Bac-NP as a new and improved gene delivery system for therapeutic applications.
authors.affiliation: Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering and Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Arghya
authors.initials: A
authors.lastname: Paul
authors.forename: Zyad M
authors.initials: ZM
authors.lastname: Binsalamah
authors.forename: Afshan A
authors.initials: AA
authors.lastname: Khan
authors.forename: Sana
authors.initials: S
authors.lastname: Abbasia
authors.forename: Cynthia B
authors.initials: CB
authors.lastname: Elias
authors.forename: Dominique
authors.initials: D
authors.lastname: Shum-Tim
authors.forename: Satya
authors.initials: S
authors.lastname: Prakash
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics* / Q000627:therapeutic use*; D000818:Animals; D016367:Baculoviridae / Q000235:genetics*; D002633:Chemotaxis; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D015696:Gene Products, tat / Q000378:metabolism*; D015316:Genetic Therapy; D006334:Heart Function Tests; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008938:Mitosis; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry*; D018919:Neovascularization, Physiologic; D038081:Organogenesis; D051381:Rats; D011995:Recombination, Genetic / Q000235:genetics*; D014161:Transduction, Genetic; D019076:Transgenes / Q000235:genetics
chemical_list: D042683:Angiopoietin-1; D015696:Gene Products, tat; D004247:DNA