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-NPAng1 showed 1.75 times higher and sustained Ang-1 expression in cardiomyocytes than BacAng1, 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 AMI, data showed increase in capillary density (p < 0.01) and reduction in infarct sizes (p < 0.05) in Bac-NPAng1 compared to BacAng1, NPAng1 and control groups due to enhanced myocardial Ang-1 expression at peri-infarct regions (1.65 times higher than BacAng1). Furthermore, the Bac-NPAng1 group showed significantly higher cardiac performance in echocardiography than BacAng1 (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. [Copyright &y& Elsevier]