Baculovirus-mediated gene transfer in the presence of human serum or blood facilitated by inhibition of the complement system

Hofmann, Christian; Strauß, Michael

doi:10.1038/sj.gt.3300607

Cited by 142 publications

(130 citation statements)

References 31 publications

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“…A major drawback in the use of baculovirus vectors for in vivo gene therapy is the inactivation of baculoviruses by the complement system. 56 Complement inactivation of baculoviruses can be overcome by the depletion of viral neutralizing factors in the sera prior to baculovirus infection. 12,56,57 The effects of the complement system have also been overcome by the generation of complement-resistant baculoviruses.…”

Section: Discussionmentioning

confidence: 99%

“…56 Complement inactivation of baculoviruses can be overcome by the depletion of viral neutralizing factors in the sera prior to baculovirus infection. 12,56,57 The effects of the complement system have also been overcome by the generation of complement-resistant baculoviruses. 58 In order to test the efficacy of baculovirus vectors prior to in vivo gene therapy, an in vitro system of baculovirusmediated gene transfer with similar hepatocyte biology to the in vivo liver must be established.…”

Section: Discussionmentioning

confidence: 99%

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Role of paracellular junction complexes in baculovirus-mediated gene transfer to nondividing rat hepatocytes

et al. 2003

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Gene delivery to differentiated hepatocytes is notoriously difficult. Hepatocytes plated on collagen-coated dishes and maintained in dimethyl sulfoxide (DMSO)-supplemented medium acquire paracellular junctions, arrange themselves in multicellular islands and are an excellent in vitro model for studying liver function. Baculovirus-mediated gene delivery to hepatocytes in this culture system is restricted to peripheral cells of the islands. However, this limitation can be overcome by transient calcium depletion of the cells prior to and during baculovirus infection. Examination of the mechanism underlying this process revealed that calcium depletion was accompanied by a transient loss of intercellular contacts and paracellular junction complex integrity, increased distance between adjoining cells, and internalization of the tight junction protein, zona occludens ZO-1.Internalization of ZO-1 was accompanied by baculovirus infection of internal cells of hepatocyte islands. When calcium levels were restored, paracellular junction complex integrity returned to normal by 12 h. No permanent alterations in hepatocyte ultrastructure and albumin mRNA, and protein expression were caused by this gene transfer method. Loss in paracellular junction complex integrity exposes the basolateral (sinusoidal) surface of hepatocytes resulting in homogeneous baculovirus-mediated gene delivery to approximately 75% of the cells in long-term DMSO culture. We conclude that the use of recombinant baculovirus as a vector in combination with transient calcium depletion is a highly efficient method for delivering exogenous genes to hepatocytes without loss of hepatic differentiation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Role of paracellular junction complexes in baculovirus-mediated gene transfer to nondividing rat hepatocytes

et al. 2003

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“…It has been reported that baculovirus vectors produced in insect cells are sensitive to substantial inactivation in vitro by human, rat and guinea-pig serum, and that the vectors have extremely poor infectivity in vivo in mice and rats due to complement inactivation. [28][29][30] By testing gp64-pseudotyped lentiviral vectors, whether the complement sensitivity of baculovirus vectors in rodent serum is due to recognition of the specific envelope glycoprotein or the insect-derived lipid envelope could be evaluated. In this study, the gp64-pseudotyped lentiviral vectors were not inactivated by serum from C57BL/6 mice or Nude rats (Figure 5b).…”

Section: Gp64-pseudotyped Lentiviral Vectors In Vivomentioning

confidence: 99%

Lentiviral vectors pseudotyped with baculovirus gp64 efficiently transduce mouse cells in vivo and show tropism restriction against hematopoietic cell types in vitro

et al. 2004

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“…14 A shortcoming of these vectors is that they are quickly inactivated by human serum and rodent serum, precluding their effective use in vivo. 15,16 It was proposed that inactivation of these vectors was triggered by human and rodent recognition of insect-specific glycosylation epitopes on the membrane envelope of the vector. 15,17 However, we recently found that lentiviral vectors produced in human cells and pseudotyped with gp64, the major envelope protein of baculovirus, are still inactivated by serum complement from humans but not rodents.…”

Section: Introductionmentioning

confidence: 99%

“…15,16 It was proposed that inactivation of these vectors was triggered by human and rodent recognition of insect-specific glycosylation epitopes on the membrane envelope of the vector. 15,17 However, we recently found that lentiviral vectors produced in human cells and pseudotyped with gp64, the major envelope protein of baculovirus, are still inactivated by serum complement from humans but not rodents. 3 This result indicated that at least some component of baculovirus inactivation in human serum is specific to the gp64 protein and not the insect-derived envelope.…”

Section: Introductionmentioning

confidence: 99%

Complement regulatory proteins are incorporated into lentiviral vectors and protect particles against complement inactivation

et al. 2004

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Lentiviral vectors pseudotyped with G glycoprotein from vesicular stomatitis virus (VSV-G) and baculovirus gp64 are inactivated by human complement. The extent of vector inactivation in serum from individual donors was examined and results showed wide donor-dependent variation in complement sensitivity for VSV-G-pseudotyped lentivectors. Amphotropic envelope (Ampho)-pseudotyped vectors were generally resistant to serum from all donors, while gp64-pseudotyped vectors were inactivated but showed less donor-to-donor variation than VSV-G. In animal sera, the vectors were mostly resistant to inactivation by rodent complement, whereas canine complement caused a moderate reduction in titer. In a novel advance for the lentiviral vector system, human complement-resistant-pseudotyped lentivector particles were produced through incorporation of complement regulatory proteins (CRPs). Decay accelerating factor (DAF)/CD55 provided the most effective protection using this method, while membrane cofactor protein (MCP)/ CD46 showed donor-dependent protection and CD59 provided little or no protection against complement inactivation. Unlike previous approaches using CRPs to produce complement-resistant viral vectors, CRP-containing lentivectors particles were generated for this study without engineering the CRP molecules. Thus, through overexpression of native DAF/CD55 in the viral producer cell, an easy method was developed for generation of lentiviral vectors that are almost completely resistant to inactivation by human complement. Production of complement-resistant lentiviral particles is a critical step toward use of these vectors for in vivo gene therapy applications. Gene Therapy (2005) 12, 238-245.

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Baculovirus-mediated gene transfer in the presence of human serum or blood facilitated by inhibition of the complement system

Cited by 142 publications

References 31 publications

Role of paracellular junction complexes in baculovirus-mediated gene transfer to nondividing rat hepatocytes

Role of paracellular junction complexes in baculovirus-mediated gene transfer to nondividing rat hepatocytes

Lentiviral vectors pseudotyped with baculovirus gp64 efficiently transduce mouse cells in vivo and show tropism restriction against hematopoietic cell types in vitro

Complement regulatory proteins are incorporated into lentiviral vectors and protect particles against complement inactivation

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