Baculoviruses exhibit restricted cell type specificity in rat brain: a comparison of baculovirus- and adenovirus-mediated intracerebral gene transfer in vivo

Lehtolainen, Pauliina; Tyynelä, Kristiina; Kannasto, J; Airenne, Kari J.; Ylä‐Herttuala, Seppo

doi:10.1038/sj.gt.3301854

Cited by 89 publications

(96 citation statements)

References 23 publications

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“…In addition, some gene expression could be detected in endothelial cells of the microvessels and in the subarachnoidal space. 4 In the present study, the LacZ control virus showed expected transduction patterns after intraventricular injections ( Figure 7). However, with the VSV-GED virus, a strong LacZ marker gene expression was also found in the epithelial lining of the lateral ventricles, epithelial lining of the cerebral aqueduct and subarachnoidal membrane ( Figure 7).…”

Section: Improved Transduction In Vivosupporting

confidence: 65%

“…The rabbits were killed 6 days after the gene transfer and muscles were fixed as described above, washed in PBS for 2 h, frozen in liquid nitrogen-cooled isopentane and cryosectioned. X-gal staining was performed as described, 4 followed by Mayer's Carmalum counterstaining. For statistical analysis, 25 slides with two tissue sections on each slide were prepared from each animal.…”

Section: Transduction Of Rabbit Musclementioning

confidence: 99%

“…They have been shown to transduce various cell types in vitro and in vivo with significant efficiency. [2][3][4][5] However, efficient gene delivery still remains a challenge for baculovirus as for other gene therapy vectors in many target cells. Efficient transduction would allow high transgene expression with a lower viral load.…”

Section: Introductionmentioning

confidence: 99%

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Truncated vesicular stomatitis virus G protein improves baculovirus transduction efficiency in vitro and in vivo

et al. 2005

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Section: Improved Transduction In Vivosupporting

confidence: 65%

Section: Transduction Of Rabbit Musclementioning

confidence: 99%

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Truncated vesicular stomatitis virus G protein improves baculovirus transduction efficiency in vitro and in vivo

et al. 2005

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“…6,9 It is worth noting that the brain injection does not offer cell-type specificity: in addition to astrocytes, other types of cells in the brain, including neurons, can be transduced by the injected baculoviruses. 6,[9][10][11] To restrict transgene expression to astrocytes, the promoter of the glial fibrillary acidic protein (GFAP) has been widely used. 12 With its cellular authentic sequence, the promoter is less sensitive to promoter silencing as compared to viral promoters, thus being potentially useful for long-term expression.…”

Section: Introductionmentioning

confidence: 99%

Astrocytic expression of transgene in the rat brain mediated by baculovirus vectors containing an astrocyte-specific promoter

Wang

2006

Gene Ther

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Therapeutic gene expression in glial cells has been tested for the treatment of neurological diseases in animal models. Many of such studies used the promoter of the glial fibrillary acidic protein (GFAP) to restrict gene expression to astrocytes. We have investigated in the current study whether it is possible to improve the transcriptional activity of the cellular promoter, while maintaining its cell-type specificity. We constructed an expression cassette containing a hybrid cytomegalovirus (CMV) enhancer/GFAP promoter and placed it into baculovirus vectors, a type of viral vectors capable of transducing astrocytes. In another vector design, we used inverted terminal repeats (ITRs) from adeno-associated virus (AAV) to flank the expression cassette. The recombinant baculoviruses with the hybrid promoter improved gene expression levels over two orders of magnitude in glial cell lines and by 10-fold in the rat brain when compared to the baculoviruses with the GFAP promoter alone. The expression was further improved by ITR flanking, reaching levels higher than that mediated by the baculovirus vectors with the CMV immediate-early enhancer/ promoter (CMV promoter). Using these recombinant baculoviruses, we observed extended in vivo transgene expression in the rat brain at 90 days postinjection, by which time the gene expression from baculovirus vectors with the GFAP or CMV promoter had already become undetectable. The astrocyte specificity of the GFAP promoter was preserved in the engineered expression cassette with the CMV enhancer and the AAV ITRs, as demonstrated by immunohistological analysis of brain samples and an axonal retrograde transport assay. Taken together, our findings suggest that these baculovirus vectors may serve as useful tools for astrocyte-specific gene expression in the brain.

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“…The bladder local administration resulted in local expression and localization of DNA (only one kidney and one ureter among the three studied mice tested positive). On the contrary, in another local route, intracerebral administration of AdV resulted in wide ectopic distribution 35 in the spleen, heart and lung, with transgene expression (LacZ) in the heart. This study was carried out in rats using 3 Â 10 8 PFU of vector.…”

Section: Biodistribution Of Vectors Using Radioactive Tracersmentioning

confidence: 99%

Gene transfer vector biodistribution: pivotal safety studies in clinical gene therapy development

Gonin

Gaillard

2004

Gene Ther

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Techniques allowing for gene transfer vectors biodistribution investigation, in the frame of preclinical gene therapy development, are exposed. Emphasis is given on validation and test performance assessment. In the second part, specific gene vector distribution properties are reviewed (adenovirus, AAV, plasmid, retroviruses, herpes-derived vectors, germline transmission risks). The rationale for biodistribution by quantitative PCR, animal study and result interpretation is discussed. The importance and pivotal role of biodistribution study in gene transfer medicine development is shown through the determination of target organs for toxicity, germline transmission assessment and determination of risks of shedding and spreading of vectors in the gene transfer recipient and the environment.

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Baculoviruses exhibit restricted cell type specificity in rat brain: a comparison of baculovirus- and adenovirus-mediated intracerebral gene transfer in vivo

Cited by 89 publications

References 23 publications

Truncated vesicular stomatitis virus G protein improves baculovirus transduction efficiency in vitro and in vivo

Truncated vesicular stomatitis virus G protein improves baculovirus transduction efficiency in vitro and in vivo

Astrocytic expression of transgene in the rat brain mediated by baculovirus vectors containing an astrocyte-specific promoter

Gene transfer vector biodistribution: pivotal safety studies in clinical gene therapy development

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