Development of a novel bivalent baculovirus vectors for complement resistance and sustained transgene expression and its application in anti-angiogenesis gene therapy

Publication date: March 2020Source: Biomedicine &Pharmacotherapy, Volume 123Author(s): Zhisheng Wang, Mengting Li, Yonggan Ji, Mengmeng Yang, Wen Yang, Jinbao Wang, Wei LiAbstractBaculovirus (BV) is a potential gene delivery vector but only mediates transient transgene expression and easily inactivated by human complement. To this end, we intend to develop a novel bivalent BV vector for complement resistance and sustained transgene expression, and evaluate its effect in anti-angiogenesis gene therapy. The results showed that the hybrid bivalent BV significantly prolonged the expression of enhanced green fluorescent protein (eGFP) in vitro for at least 90 days at over 109 a.u. total fluorescence intensity, and exhibited significantly higher complement resistance. The control BV-mediated eGFP expression gradually declined within 15 days and showed lower transduction efficiency. In vivo studies confirmed that the hybrid bivalent BV exhibited longer duration of eGFP expression and higher transduction efficacy than the control BVs. Based on these findings, we further constructed a hybrid BV expressing the antiangiogenic fusion protein containing human endostatin and angiostatin (hEA). The hybrid BV-expressed hEA significantly prolonged the expression level of hEA with enhanced anti-angiogenic activities compared to the control groups, as evidenced by ELISA, cell proliferation, migration and tubular formation assays. With the stable expression of hEA, the hybrid BV conferred hE...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research

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Molecular PharmaceuticsDOI: 10.1021/acs.molpharmaceut.9b00983
Source: Molecular Pharmaceutics - Category: Drugs & Pharmacology Authors: Source Type: research
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Source: Current Gene Therapy - Category: Genetics & Stem Cells Authors: Tags: Curr Gene Ther Source Type: research
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Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research
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Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research
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Source: Current Gene Therapy - Category: Genetics & Stem Cells Authors: Tags: Curr Gene Ther Source Type: research
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