2007
DOI: 10.1038/sj.gt.3302940
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Localized viral vector delivery to enhance in situ regenerative gene therapy

Abstract: A lyophilization method was developed to locally release adenoviral vectors directly from biomaterials for in situ regenerative gene therapy. Adenovirus expressing a b-galactosidase reporter gene (AdLacZ) was mixed with different excipient formulations and lyophilized on hydroxyapatite (HA) disks followed by fibroblasts culturing and 5-bromo-4-chloro-3-indolyl-b-D-galactopyranoside (X-gal) staining, suggesting 1 M sucrose in phosphate-buffered saline had best viability. Adenovirus release studies showed that g… Show more

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Cited by 74 publications
(80 citation statements)
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References 41 publications
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“…Our findings extend previous work showing biomaterialmediated gene delivery using viral vectors (20,(40)(41)(42)(43)(44)(45)(46)(47)(48)(49). The majority of this work demonstrated the ability to specify the spatial location of delivered vectors, rather than the induction of tissuespecific differentiation.…”
Section: Discussionsupporting
confidence: 75%
“…Our findings extend previous work showing biomaterialmediated gene delivery using viral vectors (20,(40)(41)(42)(43)(44)(45)(46)(47)(48)(49). The majority of this work demonstrated the ability to specify the spatial location of delivered vectors, rather than the induction of tissuespecific differentiation.…”
Section: Discussionsupporting
confidence: 75%
“…17,18,27 Our previous study showed that lyophilization of rAAV onto bone allografts and stainlesssteel pins achieved gene expression with activity retained for up to 3 weeks in storage at À808C. 18 Here, we have demonstrated that rAAV can induce gene expression after lyophilization onto three commercially available bone-related biomaterials.…”
Section: Discussionmentioning
confidence: 99%
“…Lyophilized adenovirus can be precisely localized in defined patterns, and lyophilized adenovirus-expressing BMP-2 (AdBMP-2) in gelatin sponges induces more bone formation than free-form delivery of AdBMP-2. 17 The major problem of viral gene delivery is the possible adverse systemic effects of most viruses. One rare exception is recombinant adeno-associated virus (rAAV) vectors.…”
mentioning
confidence: 99%
“…Even the viral systems display a loss of activity at 4°C; for example, $85% loss of activity was seen after 1 month with an AV system lyophilized into scaffolds, and no infectivity after 2 weeks in solution. (117) This loss of activity is expected to be accelerated at the physiological temperature. (118) Various methods to stabilize viral particles during freezing and lyophilisation were reported, (118,119) but these methods offer no solution to in vivo changes in infectivity.…”
Section: Journal Of Bone and Mineral Researchmentioning
confidence: 99%
“…Bone induction via endochondral ossification was observed in hindlimb muscle of immunocompetent rats (101,102) Viral particles delivered on hydroxyapatite scaffold to the back muscles of immunocompetent rats led to bone formation (103) Bone formation in thigh muscle after delivery of a tetracycline-sensitive expression system was observed in mice only when a tetracycline analogue was administered (153) Orthotopic AV Increased regeneration in a mandibular distraction osteogenesis model in rats (154) Increased bone regeneration in an osteoporotic fracture model in tibia of sheep (155) Bone formation or increased regeneration was observed in several defect models, including a critical-size mandibular defect, (33) critical-size nasal defect in athymic nude mice, (156) rib defect in horses, (157) metatarsal defect in horses, (158) and femoral critical-size defect in rats (159) Injected AVs led to partial regeneration of critical-size calvarial defects in rats, with a more vigorous response when particles were delivered in a gelatin scaffold (117) Healing of iliac crest critical-size defects in sheep was delayed compared with no treatment when viral particles were injected to injury site (160) Bone formation was observed in a dental model in immunocompetent dogs (107) Enhanced cartilage and subchondral bone was observed in femur condyle defect in immunocompetent ponies (161) Delaying administration of viral particles improved healing of femur critical-size defects in rats (162) …”
Section: Aavmentioning
confidence: 99%