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Review
. 2011 Nov-Dec;29(6):618-31.
doi: 10.1016/j.biotechadv.2011.04.004. Epub 2011 Apr 28.

Baculovirus as a gene delivery vector: recent understandings of molecular alterations in transduced cells and latest applications

Chi-Yuan Chen  1 , Chin-Yu Lin, Guan-Yu Chen, Yu-Chen Hu
Affiliations
Review

Baculovirus as a gene delivery vector: recent understandings of molecular alterations in transduced cells and latest applications

Chi-Yuan Chen et al. Biotechnol Adv. 2011 Nov-Dec.

Abstract

Baculovirus infects insects in nature and is non-pathogenic to humans, but can transduce a broad range of mammalian and avian cells. Thanks to the biosafety, large cloning capacity, low cytotoxicity and non-replication nature in the transduced cells as well as the ease of manipulation and production, baculovirus has gained explosive popularity as a gene delivery vector for a wide variety of applications. This article extensively reviews the recent understandings of the molecular mechanisms pertinent to baculovirus entry and cellular responses, and covers the latest advances in the vector improvements and applications, with special emphasis on antiviral therapy, cancer therapy, regenerative medicine and vaccine.

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Figures

Fig. 1
Fig. 1
Baculovirus transduction of mouse induced pluripotent stem cells (iPSCs). (A) Microscopic observations. (B) Flow cytometry analyses. The cells were mock-transduced (Mock group) or transduced with a baculovirus expressing DsRed (red fluorescent protein) under the elongation factor-1α promoter at a multiplicity of infection (MOI) of 100 (BV group). The cells were observed under the phase contrast microscope or fluorescence microscope at 1 and 3 days post-transduction or detached for flow cytometry at 1 day post-transduction. The microscopic observations illustrated that baculovirus efficiently transduced iPSCs and expressed DsRed, without impairing the formation of embryonic body (EB) at day 3. The baculovirus transduction efficiency reached ≈ 45% as depicted by the flow cytometry data.
Fig. 2
Fig. 2
The ASCs engineered with the hybrid baculovirus augment the healing of massive bone defects. The NZW rabbit ASCs were transduced with the hybrid baculovirus vectors conferring sustained expression of BMP-2 or VEGF, mixed at a number ratio of 4:1, loaded into cylindrical PLGA scaffolds (1.5 × 106 cells/scaffold) and implanted to the critical-size segmental defects at the femora of NZW rabbits (2 constructs/defect, designated L group). The S group contained ASCs that were transduced with conventional baculoviruses transiently expressing BMP-2/VEGF and implanted in a similar fashion. The Mock group comprised the mock-transduced ASCs as the negative control. X-ray radiography, gross appearance examination, micro computed tomography (μCT), hematoxylin and eosin (H&E) staining and CD 31-specific immunohistochemical staining (to detect blood vessel formation) performed at 12 weeks post-implantation collectively demonstrated that the L group (persistently expressing BMP-2 and VEGF) resulted in significantly improved bone healing and angiogenesis in comparison with the S group (transiently expressing BMP-2 and VEGF) and Mock group. Stars indicate the new bone while arrows indicate the blood vessel formation.
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