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. 2020 Aug 11;12(8):759. doi: 10.3390/pharmaceutics12080759

Table 1.

Known challenges to baculovirus administration in vivo and a summary of strategies to overcome them.

Baculovirus in Vivo Delivery Challenges Approaches to Overcome Issue
Narrow tropism
(e.g., target cells or tissue are not efficiently transduced)		 Pseudotyping can be used to change or expand cell tropism:

  • Vescicular stomatitis virus glycoprotein, VSV-G [19,66,67,68];

  • Rabies virus glyprotein RVG [69];

  • Cell-type specific peptides [70];

  • Thogoto and Dori virus envelope proteins [71];

  • Gp64 mutants [58].
Serum complement-mediated inactivation
Baculovirus is inactivated by human serum complement-cascade		 Pseudotyping with complement shielding factors can enhance viral stability in the bloodstream:

  • Decay accelerating factor (DAF) [72];

  • Chimeric DAF fused to complement regulatory factors [73].

Chemical modifications have been reported to enhance serum resistance:

  • Polyethylene glycol (PEG) coating [62];

  • Polyethylenimine (PEI) coating [60,61].
Intracellular immune response inactivation
Baculovirus efficiently reaches target cells but is rapidly inactivated and silenced by intracellular immune response pathways.		 Histone deacetylases (HDACs) inhibitors can be used ex vivo to counteract silencing. Due to broad spectra and high toxicity they cannot be used systemically:
•Valproic acid (VPA) or sodium butyrate (NaBu) [74,75].
Genetically encoded intracellular immune suppression strategies increase transgene expression:

  • Ablation of STING, TBK1, IRF3, or IPS-1 [76];

  • RNA interference of RIPK1 [77];

  • Viral proteins with intracellular immuno-suppressive activity (NS3/4a protease from Hepatitis C virus) [76].