A nanobiohybrid complex of recombinant baculovirus and Tat/DNA nanoparticles for delivery of Ang-1 transgene in myocardial infarction therapy

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-NPAng1 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-NPAng1 to AMI rat model. 3 weeks post AM1, data showed increase in capillary density (p < 0.01) and reduction in infarct sizes (p < 0.05) in Bac-NPAng1 compared to Bac(Ang1), NPAng1 and control groups due to enhanced myocardial Ang-1 expression at pertinfarct regions (1.65 times higher than Bac(Ang1)). Furthermore, the Bac-NPAng1 group showed significantly higher cardiac performance in echocardiography than Bac(Ang1) (44.2 +/- 4.77% vs 37.46 +/- 5.2%, p < 0.01), NPAng1 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. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.