Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone morphogenetic proteins (BMPs) are well-established agents for inducing orthotopic and ectopic bone formation. However, their clinical usefulness as regenerative agents may be limited by a short in vivo half-life and low specific activity. BMP gene therapy is an alternative route for exploiting the bone-inductive activity of this class of molecules. To test the feasibility of this approach, we examined the osteogenic activity of AdCMV-BMP7, an adenovirus containing BMP7 cDNA under control of the CMV promoter that was constructed using Cre/lox recombination (Hardy et al. [1997] J. Virol. 71:1842-1849). Adenovirus vectors were shown to readily infect a wide variety of cell types in vitro including osteoblasts, fibroblasts, and myoblasts. COS7 cells transduced with AdCMV-BMP7 produced high levels of BMP-7 (approximately 0.5 microg/10(6) cells). Furthermore, transduction of C2C12 murine myoblast cells with AdCMVBMP-7 suppressed the muscle phenotype and induced in vitro osteoblast differentiation. To test its in vivo biological activity, AdCMV-BMP7 was mixed with a bovine bone-derived collagen carrier (10(8) plaque-forming units virus/site) and was implanted into mouse muscle and dermal pouches. In both cases, an ossicle containing cortical and trabecular bone and a clearly defined marrow cavity formed at the site of virus implantation within 4 weeks. These data demonstrate that AdCMV-BMP7 transduced cells produce biologically active BMP-7 both in vitro and in vivo and show that gene therapy by direct viral transduction using a virus/matrix implant may be a viable route for stimulating bone regeneration.
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PMID:Gene therapy for bone formation: in vitro and in vivo osteogenic activity of an adenovirus expressing BMP7. 1086 45

Localized gene delivery for repair of bone defects requires appropriate carriers for the gene therapy vectors. The objective of this study was to determine if hydrogels can control temporal and spatial delivery of adenovirus for localized gene therapy. Adenovirus expressing beta-galactosidase was suspended in liquid or fibrin or collagen gels of varied concentrations and incubated prior to testing its bioactivity. The bioactivity of the virus was determined by exposing fibroblasts to the medium, the gels, or the elution medium from the gels. Bioactivity of adenovirus suspended in medium or collagen decreased to half-maximal activity after 15 h of incubation. In contrast, virus suspended in fibrin exhibited a threefold extension of bioactivity and did not reach half-maximal activity for 45 h. Bioactivity of adenovirus in hydrogels was determined to be a function of the gel concentration. In vivo experiments involved intramuscular implantation of BMP-7-expressing adenovirus in collagen, fibrin, or liquid in nude mice for 1, 2, or 4 weeks. Bone formation was observed only after 4 weeks, with bone formation occurring in 80% of muscles implanted with fibrin or collagen and 50% of muscles implanted with liquid. Fibrin gel also led to significantly larger ossicles, indicating that fibrin may offer protection from loss of infectivity both in vivo and in vitro. These results demonstrated that hydrogels may be used as carriers to control delivery of the virus and resultant tissue regeneration.
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PMID:Delivery and protection of adenoviruses using biocompatible hydrogels for localized gene therapy. 1474 86