Future Aspects

Strong evidence now exists to support baculovirus-mediated gene delivery in vitro, and there is very little doubt that this concept is also useful for in vivo. The genuine advantages of baculovirus vector (Table 1) certainly make it a potential new player in gene therapy. However, before this, further studies concerning AcMNPV behavior in mammals, particularly biodistribution and inflammatory issues, need to be studied.

An ideal gene therapy vector should transduce only the desired target cells with a high efficacy. Therefore, a strong interest in developing targeted gene delivery vectors has emerged (155-162). As a first step toward targeted baculovirus transduction, Ojala et al. (163) recently described baculovirus vectors displaying either a functional single chain antibody fragment (scFv) specific for the carcinoembryonic antigen or the synthetic IgG-binding domains derived from protein A of Staphylococcus aureus. Display of the targeting moieties on the viral surface was achieved through fusion to the N-terminus of gp64 (Fig. 2) (121). Specific binding of the gp64 fusion viruses to mammalian target cells could be demonstrated by fluorescence and confocal microscopy. However, no enhancement of the viral entry or gene transfer into the mammalian cells could be observed by monitoring GFP expression. Indeed, it is well known that a specific ligand-re-ceptor interaction does not necessarily guarantee efficient transduction of the target cells (161). Internalization, escape from endosomes, and transport of the genetic material into the nucleus are required as well (28,164). The fact that bacu-loviruses seem to not have any blocks in the entry into the cells (11,12,131,141,165), may make baculovirus targeting

Table 3 Summary of Current Data of Baculovirus-mediated Gene Transfer In Vivo

Study

Target animal

Positive organ/tissue

Positive cell types

Notes

Airenne et al. (5)

Rabbits

Blood vessel,

Fibroblasts, smooth muscle

Collar device used for

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