Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
|---|
| delivery of alpha- and beta-sarcoglycan by recombinant adeno-associated virus: efficient rescue of muscle, but differential toxicity. | the sarcoglycanopathies are a group of four autosomal recessive limb girdle muscular dystrophies (lgmd 2d, 2e, 2c, and 2f), caused by mutations of the alpha-, beta-, gamma-, or delta-sarcoglycan genes, respectively. the delta-sarcoglycan-deficient hamster has been the most utilized model for gene delivery to muscle by recombinant adeno-associated virus (aav) vectors; however, human patients with delta-sarcoglycan deficiency are exceedingly rare, with only two patients described in the united sta ... | 2002 | 12228018 |
| intramuscular administration of recombinant adeno-associated virus 2 alpha-1 antitrypsin (raav-serpina1) vectors in a nonhuman primate model: safety and immunologic aspects. | we performed a series of studies in baboons to evaluate the safety of intramuscular administration of raav vector expressing the alpha-1 antitrypsin (aat) gene (serpina1) in a nonhuman primate model. initial experiments performed with an raav vector expressing the human serpina1 gene (at doses of up to 5 x 10(12) vector genomes/kg) resulted in the generation of anti-human aat antibodies, which correlated with a loss of detectable transgene expression. subsequent studies made use of the baboon se ... | 2002 | 12231168 |
| a single-subunit nadh-quinone oxidoreductase renders resistance to mammalian nerve cells against complex i inhibition. | numerous studies suggest that dysfunction of mitochondrial proton-translocating nadh-ubiquinone oxidoreductase (complex i) is associated with neurodegenerative disorders, such as parkinson's disease and huntington's disease. development of methods to correct complex i defects seems important. we have previously shown that the single-subunit nadh dehydrogenase of saccharomyces cerevisiae (ndi1p) can work as a replacement for complex i in mammalian cells. using a recombinant adeno-associated virus ... | 2002 | 12231169 |
| gene therapy for pyruvate dehydrogenase e1alpha deficiency using recombinant adeno-associated virus 2 (raav2) vectors. | to determine the feasibility of gene transfer to correct defects in the e1alpha subunit of the pyruvate dehydrogenase (pdh) complex (pdc), we constructed raav vectors that expressed pdh e1alpha, either alone or with a green fluorescent protein tag, from a hybrid cytomegalovirus (cmv) enhancer/chicken beta-actin (cb) promoter. these vectors were functional in vitro, as judged by increased expression of mrna in vector-transduced deficient cell lines and correction of the biochemical defect in pdh ... | 2002 | 12231176 |
| lymphangiogenic gene therapy with minimal blood vascular side effects. | recent work from many laboratories has demonstrated that the vascular endothelial growth factor-c/vegf-d/vegfr-3 signaling pathway is crucial for lymphangiogenesis, and that mutations of the vegfr3 gene are associated with hereditary lymphedema. furthermore, vegf-c gene transfer to the skin of mice with lymphedema induced a regeneration of the cutaneous lymphatic vessel network. however, as is the case with vegf, high levels of vegf-c cause blood vessel growth and leakiness, resulting in tissue ... | 2002 | 12235206 |
| development of multiple cloning site cis-vectors for recombinant adeno-associated virus production. | recombinant adeno-associated virus (raav) has become a very popular gene therapy vector in the past several years. a cis-plasmid is used to generate the raav stocks. in this plasmid, the entire expression cassette is incorporated between two aav inverted terminal repeats. the construction of cis-plasmid has been problematic because of the high-frequency recombination of the viral inverted terminal repeats. here we describe the design and construction of several multiple cloning site cis-plasmids ... | 2002 | 12238777 |
| bronchoalveolar fluid is not a major hindrance to virus-mediated gene therapy in cystic fibrosis. | successfully targeting the airway epithelium is essential for gene therapy of some pulmonary diseases. however, the airway epithelium is resistant to virus-mediated gene transfer with commonly used vectors. vectors that interact with endogenously expressed receptors on the apical surface significantly increase gene transfer efficiency. however, other endogenous components involved in host immunity may hinder virus-mediated gene transfer. we tested the effect of bronchoalveolar lavage liquid (bal ... | 2002 | 12239320 |
| improved hepatic gene transfer by using an adeno-associated virus serotype 5 vector. | adeno-associated viral (aav) vectors have been shown to direct stable gene transfer and expression in hepatocytes, which makes them attractive tools for treatment of inherited disorders such as hemophilia b. while substantial levels of coagulation factor ix (f.ix) have been achieved using aav serotype 2 vectors, use of a serotype 5 vector further improves transduction efficiency and levels of f.ix transgene expression by 3- to 10-fold. in addition, the aav-5 vector transduces a higher proportion ... | 2002 | 12239326 |
| primary human cells differ in their susceptibility to raav-2-mediated gene transfer and duration of reporter gene expression. | the susceptibility of a variety of different primary tissues was examined to long-term transduction with recombinant adeno-associated virus type 2 (raav-2) and factors influencing the transduction efficiency. in contrast to others using cell lines and animal models, emphasis was placed on the use of primary human cells. enhanced green fluorescent protein (egfp) marker gene expression was examined using fluorescence-activated cell sorting analysis. the most effective target cells for raav-2-media ... | 2002 | 12270659 |
| development and optimization of a real-time quantitative pcr-based method for the titration of aav-2 vector stocks. | despite the clinical application of adeno-associated virus (aav) gene therapy, the titration of viral stocks has not yet been standardized. this complicates the comparison of viral stocks between laboratories. functional titering of aav is time-consuming, requires the manipulation of hazardous material, and often has a high degree of variability. we established an optimized real-time quantitative polymerase chain reaction (rq-pcr) titration assay to determine viral titers and compared it with a ... | 2002 | 12349826 |
| adeno-associated virus-mediated osteoprotegerin gene transfer protects against particulate polyethylene-induced osteolysis in a murine model. | osteoprotegerin (opg), a natural negative regulator of osteoclastogenesis and bone resorption, may be a potential therapeutic agent for treatment of osteolysis-associated prosthetic joint loosening. using an in vivo adeno-associated virus (aav)-mediated gene transfer technique, this study was designed to evaluate the protective effects of opg transgene against orthopedic wear debris-induced bone loss in a murine model of osteolysis. | 2002 | 12355500 |
| overexpression of parkinson's disease-associated alpha-synucleina53t by recombinant adeno-associated virus in mice does not increase the vulnerability of dopaminergic neurons to mptp. | mutations in the alpha-synuclein gene are linked to a rare dominant form of familial parkinson's disease, and alpha-synuclein is aggregated in lewy bodies of both sporadic and dominant parkinson's disease. it has been proposed that mutated alpha-synuclein causes dopaminergic neuron loss by enhancing the vulnerability of these neurons to a variety of insults, including oxidative stress, apoptotic stimuli, and selective dopaminergic neurotoxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ... | 2002 | 12360578 |
| gene therapy progress and prospects: cystic fibrosis. | since the cloning of the cystic fibrosis gene (cftr) in 1989, 18 clinical trials have been carried out, including five in the 2 years reviewed here. most trials demonstrated proof-of-principle for gene transfer to the airway. however, gene transfer efficiency with each of the three gene transfer agents (adenovirus (ad), adeno-associated virus 2 (aav2) and cationic liposomes) was low, and most likely insufficient to achieve clinical benefit. here, we will review the clinical and pre-clinical prog ... | 2002 | 12364999 |
| fast and reliable titration of recombinant adeno-associated virus type-2 using quantitative real-time pcr. | in this study, a quantitative real-time pcr (qpcr) was developed to determine genomic raav-2 titers using the light-cycler technology. since the cmv promoter is the most commonly used promoter in gene therapeutic approaches, primers were designed which hybridize with the human cmv promoter sequence. pcr products were detected by the addition of sybr green. qpcr of a 5 log spanning serial dilution of the vector plasmid containing one cmv promoter per plasmid molecule yielded a high amplification ... | 2002 | 12367732 |
| efficient generation and amplification of high-capacity adeno-associated virus/adenovirus hybrid vectors. | effective gene therapy is dependent on safe gene delivery vehicles that can achieve efficient transduction and sustained transgene expression. we are developing a hybrid viral vector system that combines in a single particle the large cloning capacity and efficient cell cycle-independent nuclear gene delivery of adenovirus (ad) vectors with the long-term transgene expression and lack of viral genes of adeno-associated virus (aav) vectors. the strategy being pursued relies on coupling the aav dna ... | 2002 | 12368316 |
| [research of the anti-tumor effect of human endostatin mediated by recombinant adeno-associated virus]. | it was reported that endostatin could inhibit tumor angiogenesis, then inhibit the growth and metastasis of tumor. however, there was few report about the treatment usage of endostatin. this study was designed to explore the effect of endostatin mediated with recombinant adeno-associated virus(raav) on tumor growth and metastasis. | 2002 | 12520738 |
| vigilant vector: heart-specific promoter in an adeno-associated virus vector for cardioprotection. | repeated bouts of ischemia in the heart lead to fibrosis and eventually to heart failure. although certain genes, such as sod or hemoxygenase and antisense to at(1)r, ace, and (beta(1)-ar can provide short-term protection of the heart from ischemia, there is no known mechanism for constantly responding to repeated incidences of ischemia. we hypothesized that a "vigilant vector," designed to be expressed specifically in the heart and switch on therapeutic genes only during hypoxia, would provide ... | 2002 | 11882625 |
| gene therapy for hypertension: the preclinical data. | in spite of several drugs for the treatment of hypertension, there are many patients with poorly controlled high blood pressure. this is partly due to the fact that all available drugs are short-lasting (24 hr or less), have side effects, and are not highly specific. gene therapy offers the possibility of producing longer-lasting effects with precise specificity from the genetic design. preclinical studies on gene therapy for hypertension have taken two approaches. chao et al. have carried out e ... | 2002 | 11883075 |
| streamlined large-scale production of recombinant adeno-associated virus (raav) vectors. | 2002 | 11883083 | |
| characterization of adeno-associated virus rep protein inhibition of adenovirus e2a gene expression. | adeno-associated virus (aav) replication (rep) proteins are pleiotropic effectors of viral dna replication, rna transcription, and site-specific integration into chromosome 19. in addition to regulating aav gene expression, the rep proteins modulate expression of a variety of cellular and viral genes. in this report we investigate rep-mediated effects on expression of the adenovirus (ad) e2a gene and the ad major late promoter. we have found that all four rep proteins repress e2a expression at t ... | 2002 | 11886255 |
| viral-mediated gene transfer to mouse primary neural progenitor cells. | neural progenitor cells may provide for cell replacement or gene delivery vehicles in neurodegen-erative disease therapies. the expression of therapeutic proteins by neural progenitors would be enhanced by viral-mediated gene transfer, but the effects of several common recombinant viruses on primary progenitor cell populations have not been tested. to address this issue, we cultured cells from embryonic day 16-18 mouse brain in serum-free medium containing epidermal growth factor or basic fibrob ... | 2002 | 11786041 |
| neurological correction of lysosomal storage in a mucopolysaccharidosis iiib mouse model by adeno-associated virus-mediated gene delivery. | mucopolysaccharidosis (mps) iiib is characterized by mild somatic features and severe neurological diseases leading to premature death. no definite treatment is available for mps iiib patients. we constructed two recombinant adeno-associated virus (raav) vectors containing the human alpha-n-acetylglucosaminidase (naglu) cdna driven by either a cmv or a neuron-specific enolase (nse) promoter. in vitro, these raav vectors mediated efficient expression of recombinant naglu in human mps iiib fibrobl ... | 2002 | 11786044 |
| targeted retrograde gene delivery for neuronal protection. | the cellular heterogeneity and complex circuitry of the central nervous system make it difficult to achieve precise delivery of experimental and therapeutic agents. we report here an in vivo retrograde gene delivery strategy to target mature projection neurons using adeno-associated virus, a vector with low toxicity and the capacity for long-term gene expression. viral delivery to axon terminal fields in the hippocampus and striatum resulted in viral internalization, retrograde transport, and tr ... | 2002 | 11786045 |
| recombinant adeno-associated virus gene therapy for cystic fibrosis and alpha(1)-antitrypsin deficiency. | 2002 | 11893723 | |
| feasibility of generating adeno-associated virus packaging cell lines containing inducible adenovirus helper genes. | the adeno-associated virus (aav) vector system is based on nonpathogenic and helper-virus-dependent parvoviruses. the vector system offers safe, efficient, and long-term in vivo gene transfer in numerous tissues. clinical trials using aav vectors have demonstrated vector safety as well as efficiency. the increasing interest in the use of aav for clinical studies demands large quantities of vectors and hence a need for improvement in vector production. the commonly used transient-transfection met ... | 2002 | 11799185 |
| chromosomal effects of adeno-associated virus vector integration. | adeno-associated virus (aav) vectors are currently being used in several clinical gene-therapy trials (see the nih oba human gene transfer clinical trials database); however, little is known about the chromosomal effects of vector integration. here we report that integrated vector proviruses are associated with chromosomal deletions and other rearrangements and are frequently located on chromosome 19 (although not at the wildtype aav integration site). | 2002 | 11799395 |
| comparison of the ef-1 alpha and the cmv promoter for engineering stable tumor cell lines using recombinant adeno-associated virus. | silencing of the viral cmv immediate early enhancer promoter can be a problem in certain cell types when engineering stable cell lines. | 2002 | 12530082 |
| dynamics of transgene expression in human glioblastoma cells mediated by herpes simplex virus/adeno-associated virus amplicon vectors. | one of the challenges in gene therapy is to ensure stable transgene expression at the site of disease with a high degree of accuracy and safety. in this paper, we examine both viral and cellular elements that may affect the level of transgene expression mediated by herpes simplex virus type 1 (hsv-1) adeno-associated virus (aav) amplicon vectors. these elements include the aav inverted terminal repeats (itrs), the aav rep proteins, and the allelic status of 19q in human glioma cell lines. the la ... | 2002 | 12542846 |
| igf1 gene transfer into skeletal muscle using recombinant adeno-associated virus in a rat model of liver cirrhosis. | systemic administration of recombinant igf1 at low levels has been shown to improve hepatic function, nutritional status and testicular atrophy in rats with ccl4-induced cirrhosis. we have developed a recombinant adeno-associated (raav) viral vector containing the cdna for rat igf1 and confirmed the expression of igf1 after intramuscular injection of this vector in a rat model of liver cirrhosis. although weight of injected muscles was significantly increased in rats with mild cirrhosis, this wa ... | 2002 | 12603011 |
| gene therapy for lung neoplasms. | the field of gene therapy is still in its infancy, but significant accomplishments have been achieved. the ability to transfer genes safely and successfully into animals and patients clearly has been established. it is highly likely that in the near future, gene therapy will be shown to have clear therapeutic efficacy in diseases such as the treatment of hemophilia (using adeno-associated virus vectors) and the stimulation of angiogenesis in peripheral vascular disease and myocardial ischemia. a ... | 2002 | 11901916 |
| human herpesvirus-6 rep/u94 gene product has single-stranded dna-binding activity. | the characterization is reported of the human herpesvirus-6b (hhv-6b) rep/u94 gene, which is a homologue of the adeno-associated virus type 2 rep. in this study, a monoclonal antibody was produced against hhv-6b rep (anti-rep mab). immunofluorescence staining using the anti-rep mab showed that rep was localized to the nucleus in hhv-6-infected mt4 cells. it was first detected at 24 h post-infection (p.i.) and accumulated to higher levels by 72 h p.i. rep may be expressed only at very low levels ... | 2002 | 11907335 |
| critical issues in gene therapy for neurologic disease. | gene therapy for the nervous system is a newly emerging field with special issues related to modes of delivery, potential toxicity, and realistic expectations for treatment of this vital and highly complex tissue. this review focuses on the potential for gene delivery to the brain, as well as possible risks and benefits of these procedures. this includes discussion of appropriate vectors, such as adeno-associated virus, lentivirus, gutless adenovirus, and herpes simplex virus hybrid amplicons, a ... | 2002 | 11916483 |
| dopaminergic cell loss induced by human a30p alpha-synuclein gene transfer to the rat substantia nigra. | somatic cell gene transfer was used to express a mutant form of alpha-synuclein (alpha-syn) that is associated with parkinson's disease (pd) in the rat substantia nigra (sn), a brain region that, in humans, degenerates during pd. dna encoding the a30p mutant of human alpha-syn linked to familial pd was incorporated into an adeno-associated virus vector, which was injected into the adult rat midbrain. the cytomegalovirus/chicken beta-actin promoter was used to drive transgene expression. over a 1 ... | 2002 | 11916484 |
| reversal of motor impairments in parkinsonian rats by continuous intrastriatal delivery of l-dopa using raav-mediated gene transfer. | intrastriatal delivery of the tyrosine hydroxylase gene by viral vectors is being explored as a tool for local delivery of l-dopa in animals with lesions of the nigrostriatal pathway. the functional effects reported using this approach have been disappointing, probably because the striatal l-dopa levels attained have been too low. in the present study, we have defined a critical threshold level of l-dopa, 1.5 pmol/mg of tissue, that has to be reached to induce any significant functional effects. ... | 2002 | 11917105 |
| aav-mediated vegf gene transfer into skeletal muscle stimulates angiogenesis and improves blood flow in a rat hindlimb ischemia model. | clinical trials on therapeutic angiogenesis using vascular endothelial growth factor (vegf) are ongoing, however the benefits of these therapies are still controversial. to establish a more efficient gene transfer method for ischemic diseases, we investigated the therapeutic potential of adeno-associated virus (aav)-mediated vegf gene transfer. | 2002 | 11922909 |
| secreted and transmembrane mucins inhibit gene transfer with aav4 more efficiently than aav5. | adeno-associated virus (aav) is a promising vector for gene transfer in cystic fibrosis. aav4 and aav5 both bind to the apical surface of differentiated human airway epithelia, but only aav5 infects. both aav4 and aav5 require 2,3-linked sialic acid for binding. however, aav5 interacts with sialic acid on n-linked carbohydrates, whereas aav4 interacts with sialic acid on o-linked carbohydrates. because mucin is decorated with o-linked carbohydrates, we hypothesized that mucin binds aav4 and inhi ... | 2002 | 11925433 |
| sustained phenotypic correction of hemophilia b dogs with a factor ix null mutation by liver-directed gene therapy. | hemophilia b is an x-linked coagulopathy caused by absence of functional coagulation factor ix (fix). using adeno-associated virus (aav)-mediated, liver-directed gene therapy, we achieved long-term (> 17 months) substantial correction of canine hemophilia b in 3 of 4 animals, including 2 dogs with an fix null mutation. this was accomplished with a comparatively low dose of 1 x 10(12) vector genomes/kg. canine fix (cfix) levels rose to 5% to 12% of normal, high enough to result in nearly complete ... | 2002 | 11929752 |
| soluble flt-1 expression suppresses carcinomatous ascites in nude mice bearing ovarian cancer. | vascular endothelial growth factor (vegf), a bifunctional protein enhancing vascular permeability and stimulating endothelial growth, is thought to be responsible for fluid accumulation and angiogenesis in ascites tumors. to investigate the effects of stable expression of the soluble form of flt-1 vegf receptor (sflt-1), a known endogenous inhibitor of vegf, on the malignant ascites tumors, we cotransduced rmg-1 human ovarian cancer cells with adeno-associated virus vectors carrying the sflt-1 c ... | 2002 | 11929819 |
| adeno-associated virus vector gene transfer and sarcolemmal expression of a 144 kda micro-dystrophin effectively restores the dystrophin-associated protein complex and inhibits myofibre degeneration in nude/mdx mice. | duchenne muscular dystrophy is a severe life-threatening x-linked recessive disorder, caused by mutations in the dystrophin gene, for which currently there is no effective treatment. because of the large size of the dystrophin cdna (14 kb) this precluded it from being used in early adenovirus- or retrovirus-based gene therapy vectors. however, some therapeutic success has been achieved in mdx mice using adenovirus- and retrovirus-mediated transfer of a 6.3 kb recombinant mini-dystrophin cdna. de ... | 2002 | 11929846 |
| adeno-associated virus capsids displaying immunoglobulin-binding domains permit antibody-mediated vector retargeting to specific cell surface receptors. | recombinant adeno-associated virus type 2 (raav2) is a promising vector for human somatic gene therapy. however, its broad host range is a disadvantage for some applications, because it reduces the specificity of the gene transfer. to overcome this limitation, we sought to create a versatile raav vector targeting system which would allow us to redirect raav binding to specific cell surface receptors by simple coupling of different ligands to its capsid. for this purpose, an immunoglobulin g (igg ... | 2002 | 11932421 |
| differential activation of innate immune responses by adenovirus and adeno-associated virus vectors. | adenovirus vectors induce acute inflammation of infected tissues due to activation of the innate immune system and expression of numerous chemokines and cytokines in transduced target cells. in contrast, adeno-associated virus (aav) vectors are not associated with significant inflammation experimentally or clinically. we tested the ability of aav vectors to induce the expression of chemokines in vitro and to activate the innate immune system in vivo. in human hela cells and murine renal epitheli ... | 2002 | 11932423 |
| inhibition of retinal neovascularisation by gene transfer of soluble vegf receptor sflt-1. | retinal angiogenesis is a central feature of the leading causes of blindness. current treatments for these conditions are of limited efficacy and cause significant adverse effects. in this study, we evaluated the angiostatic effect of gene transfer of the soluble vegf receptor sflt-1 in a mouse model of ischaemia-induced retinal neovascularisation using adenovirus and adeno-associated virus (aav) vectors. we induced proliferative retinopathy in mice by exposure to 75% oxygen from postnatal day 7 ... | 2002 | 11938451 |
| recombinant adeno-associated virus serotypes 2- and 5-mediated gene transfer in the mammalian brain: quantitative analysis of heparin co-infusion. | recombinant adeno-associated viruses (raavs) are among the most promising vectors for gene delivery into the cns. however, a major hurdle for gene transfer to the mammalian brain is to achieve high transduction levels in target cells beyond the immediate injection site. therefore, building upon the optimization of injection parameters on which we have recently reported, it is important to define additional methods to increase the volume of distribution. here, we establish an optimal heparin conc ... | 2002 | 11945063 |
| central leptin gene delivery evokes persistent leptin signal transduction in young and aged-obese rats but physiological responses become attenuated over time in aged-obese rats. | the purpose of this study was to determine if long-term leptin treatment desensitizes leptin signal transduction and the subsequent downstream anorexic and thermogenic responses in normal and leptin-resistant age-related obese rats. to this end, we administered, i.c.v., recombinant adeno-associated virus encoding rat leptin cdna (raav-leptin) or control virus into young and aged-obese rats and after 9 or 46 days, examined food intake, oxygen consumption, body weight, serum leptin, stat3 phosphor ... | 2002 | 11955525 |
| adeno-associated virus vectors under scrutiny. | 2002 | 11955549 | |
| [expression of lecithin cholesterol acyltransferase and/or apoa-i mediated by recombinant adeno-associated virus in myogenic cells]. | lecithin cholesterol acyltransferase (lcat) is the major enzyme producing most plasma cholesterol esters(ce) and a key participant in the process of reverse cholesterol transfer (rct). the aim of this research is to co-express lcat and it's natural activator apoa-i, with the recombinant adeno-associated virus vectors in the skeletal muscle cells, in order to pave a new way for gene therapy of the primary or secondary lcat deficiency. 293t cells was cotransfected with pdg and raavail/raavl plasmi ... | 2002 | 11958131 |
| the vp1 capsid protein of adeno-associated virus type 2 is carrying a phospholipase a2 domain required for virus infectivity. | the unique region of the vp1 protein of parvoviruses was proposed to contain a parvoviral phospholipase a2 (pvpla2) motif. here, pla2 activity is shown in the unique region of adeno-associated virus type 2 (aav-2) vp1 when expressed as an isolated domain in bacteria. mutations in this region of the capsid protein strongly reduced the infectivity of mutant virions in comparison to wild-type aav-2. this correlated with effects on the activity of pla2. the mutations had no influence on capsid assem ... | 2002 | 11961250 |
| parvovirus-mediated gene transfer for the haemophilias. | gene therapy may revolutionize the treatment of haemophilia. effective gene therapy requires sustained therapeutic levels of factors ix (fix) and viii. adeno-associated virus (aav) is a member of the parvovirus family, is a nonpathogenic virus with a broad host cell range, and does not provoke a significant immune response upon infection. these favourable characteristics make aav a suitable gene transfer vector for factor deficient patients. a new understanding of aav biology coupled with novel ... | 2002 | 11966856 |
| adeno-associated virus-mediated transfer of human acid maltase gene results in a transient reduction of glycogen accumulation in muscle of japanese quail with acid maltase deficiency. | glycogen storage disease type ii (gsd ii), pompe's disease, is caused by the deficiency of acid alpha-d-glucosidase (gaa) in lysosome and is the most common form of gsd in taiwan. most cases are the infantile form. the disease is relentless and most patients die of cardiac failure and respiratory tract infection in the first year of life. at present, no treatment has been proved effective for this fatal disease. the applicability of enzyme replacement therapy is under investigation. however, hig ... | 2002 | 11973631 |
| [generation of a series of recombinant herpes simplex viruses which can provide replicating and packaging functions for recombinant adeno-associated virus]. | to construct a series of recombinant herpes simplex viruses that can provide replicating and packaging functions for recombinant adeno-associated virus (raav), and to select the strains possessing stronger functions for large-scale production of raav. | 2002 | 11986753 |
| highly purified recombinant adeno-associated virus vectors. preparation and quantitation. | 2002 | 11987793 | |
| high-titer stocks of adeno-associated virus from replicating amplicons and herpes vectors. | 2002 | 11987794 | |
| herpes simplex virus/adeno-associated virus hybrid vectors for gene transfer to neurons. preparation and use. | 2002 | 11987795 | |
| correction of the enzymatic and functional deficits in a model of pompe disease using adeno-associated virus vectors. | pompe disease is a lysosomal storage disease caused by the absence of acid alpha-1,4 glucosidase (gaa). the pathophysiology of pompe disease includes generalized myopathy of both cardiac and skeletal muscle. we sought to use recombinant adeno-associated virus (raav) vectors to deliver functional gaa genes in vitro and in vivo. myotubes and fibroblasts from pompe patients were transduced in vitro with raav2-gaa. at 14 days postinfection, gaa activities were at least fourfold higher than in their ... | 2002 | 11991748 |
| rep/cap gene amplification and high-yield production of aav in an a549 cell line expressing rep/cap. | cell lines stably expressing rep/cap are important tools for studying adeno-associated virus (aav) biology and producing aav vectors. several rep/cap cell lines have been isolated, each of which is based on hela cells. infection of these cell lines with adenovirus for production of aav vector is associated with substantial amplification of the rep/cap gene. concerns over the presence of human papilloma viral (hpv) sequences in hela cells may limit use of such lines for production of clinical-gra ... | 2002 | 11991756 |
| efficient integration of recombinant adeno-associated virus dna vectors requires a p5-rep sequence in cis. | the initial aim of this study was to combine attributes of adeno-associated virus (aav) and adenovirus (ad) gene therapy vectors to generate an ad-aav hybrid vector allowing efficient site-specific integration with ad vectors. in executing our experimental strategy, we found that, in addition to the known incompatibility of rep expression and ad growth, an equally large obstacle was presented by the inefficiency of the integration event when using traditional recombinant aav (raav) vectors. this ... | 2002 | 11991970 |
| expression of bcl-2 via adeno-associated virus vectors rescues thalamic neurons after visual cortex lesion in the adult rat. | lesions of the mammalian visual cortex cause the retrograde degeneration of the thalamic neurons projecting to the damaged cortex. the proto-oncogene bcl-2 is known to inhibit neuronal apoptosis induced by a variety of noxious stimuli and preserve the functional integrity of the injured cells. here we have tested whether the overexpression of bcl-2 via adeno-associated virus (aav) vectors is able to protect the neurons in the lateral geniculate nucleus after visual cortex ablation in adult rats. ... | 2002 | 11994121 |
| the adeno-associated virus type 2 rep protein regulates rna processing via interaction with the transcription template. | the adeno-associated virus type 2 (aav) large rep proteins can act to increase the ratio of spliced to unspliced aav rna when they are targeted to the transcription template via a rep binding element. the required rep binding site is both location and orientation independent; however, rep enhancement decreases as the distance between the promoter and the intron of the affected transcription unit increases. only the aav intron and an extended polyadenylation site must remain for the aav transcrip ... | 2002 | 11997501 |
| neonatal porcine pancreatic cell clusters as a potential source for transplantation in humans: characterization of proliferation, apoptosis, xenoantigen expression and gene delivery with recombinant aav. | neonatal porcine islets are characterized by reproducible isolation success and high yields, sizable advantages over adult islets. in this work we have analyzed selected phenotypic and functional characteristics of porcine neonatal islets relevant to their possible use for transplant in humans. we show that porcine islet cells proliferate in culture, and synthesize and store islet-specific hormones. proliferating beta cells can be easily identified. implant of cultured neonatal islets in immunod ... | 2002 | 12005100 |
| genome engineering using site-specific recombinases. | the targeted modification of the mammalian genome has a variety of applications in research, medicine, and biotechnology. site-specific recombinases have become significant tools in all of these areas. conditional gene targeting using site-specific recombinases has enabled the functional analysis of genes, which cannot be inactivated in the germline. the site-specific integration of adeno-associated virus, a major gene therapy vehicle, relies on the recombinase activity of the viral rep proteins ... | 2002 | 12006158 |
| [hepo transfer and expression by a recombinant adeno-associated virus vector]. | in order to achieve sustained human erythropoietin (hepo) expression in vivo for the treatment of anemias, recombinant adeno-associated virus (raav)-mediated hepo transfer was studied in this report. raav vector plasmid carrying hepo was constructed, and raav vector cell line for production of raav was also established. by using the one helper virus-one vector cell line strategy, which we reported previously, raav containing the hepo expression cassette was produced in large-scale. the resul ... | 2002 | 12006992 |
| sensitization of sarcoma cells to doxorubicin treatment by concomitant wild-type adeno-associated virus type 2 (aav-2) infection. | doxorubicin-based chemotherapy is used in the treatment of sarcomas. toxic side effects and poor response rates underline the demand for an improvement in current chemotherapeutic protocols. recently, it has been reported that parvoviruses confer various antineoplastic properties to infected cells, and that adeno-associated virus type 2 (aav-2) infection sensitizes malignant epithelial cells to radiation- or chemotherapy-based genotoxic treatment. thus, we analyzed whether aav-2 infection leads ... | 2002 | 12012001 |
| adeno-associated virus protects the retinoblastoma family of proteins from adenoviral-induced functional inactivation. | adeno-associated virus type 2 (aav) is known to inhibit virally mediated oncogenic transformation. one of the early events of adenovirus (ad) infection is the functional inactivation of cell cycle regulatory retinoblastoma (rb) family of proteins, which consists of retinoblastoma protein (prb), p107, and p130. in an effort to understand the molecular basis of anti-oncogenic properties of aav, we studied the effects of aav expression on these proteins in cells infected with ad. western blot analy ... | 2002 | 12019182 |
| expression of human factor viii by splicing between dimerized aav vectors. | adeno-associated virus (aav) is a useful vector for hemophilia gene therapy, but the limited effective packaging capacity of aav (5 kb) appears to be incompatible with factor viii (gene symbol f8) cdna (7 kb). although we previously demonstrated efficient packaging and expression of b-domain-deleted human f8 (bdd-f8) using a single aav vector, the packaging limit still excludes the use of large/strong regulatory elements. here we exploited the split aav vector technology that expands the packagi ... | 2002 | 12027555 |
| central leptin gene therapy blocks high-fat diet-induced weight gain, hyperleptinemia, and hyperinsulinemia: increase in serum ghrelin levels. | recombinant adeno-associated virus (raav), encoding either rat leptin (raav-lep) or green fluorescent protein (raav-gfp, control), was injected intracerebroventricularly in rats consuming a high-fat diet (hfd; 45 kcal%). caloric consumption and body weight were monitored weekly until the rats were killed at 9 weeks. untreated control rats consuming regular rat diet (rcd; 11 kcal%) were monitored in parallel. body weight gain was accelerated in raav-gfp + hfd control rats relative to those consum ... | 2002 | 12031959 |
| adeno-associated virus-mediated gene transfer of endostatin inhibits angiogenesis and tumor growth in vivo. | a variety of approaches has demonstrated that interfering with tumor-induced angiogenesis may be an effective strategy in cancer therapy. however, it is likely that to be most effective such strategies will require extended suppression of the angiogenic process. gene therapy offers a possible approach to achieve sustained release of a therapeutically potent transferred gene product. in the present study the angiogenesis inhibitor endostatin was expressed through a recombinant adeno-associated vi ... | 2002 | 12032662 |
| raav-mediated long-term liver-generated expression of an angiogenesis inhibitor can restrict renal tumor growth in mice. | it is now well established that tumor growth is angiogenesis dependent. inhibition of angiogenesis, therefore, is likely to be an effective anticancer approach. a gene therapy-mediated approach to the delivery of antiangiogenic agents using adeno-associated virus (aav) vectors has a number of advantages, including the potential for sustained expression. we have constructed a raav vector in which the expression of a soluble, truncated form of the vascular endothelial growth factor receptor-2 (flk ... | 2002 | 12036917 |
| immunogenicity of a p210(bcr-abl) fusion domain candidate dna vaccine targeted to dendritic cells by a recombinant adeno-associated virus vector in vitro. | chronic myelogenous leukemia (cml) is characterized by a t(9;22) translocation, which results in the expression of chimeric bcr-abl fusion oncoproteins that are necessary for oncogenesis, unique to the leukemic clones, and represent enticing targets for immunotherapy. as a strategy for the immunotherapy of cml, we constructed a recombinant adeno-associated virus vector encoding the p210(bcr-abl) b3a2 variant fusion region with flanking sequences (cwrba) and used it to express the bcr-abl fusion ... | 2002 | 12036931 |
| recombinant aav vector encoding human vegf165 enhances wound healing. | delivery of therapeutic genes represents an appealing possibility to accelerate healing of wounds that are otherwise difficult to treat, such as those in patients with metabolic disorders or infections. experimental evidence indicates that in such conditions potentiation of neo-angiogenesis at the wound site might represent an important therapeutic target. here we explore the efficacy of gene therapy of wound healing with an adeno-associated virus (aav) vector expressing the 165 amino acid isofo ... | 2002 | 12040459 |
| potential long-term inhibition of ocular neovascularisation by recombinant adeno-associated virus-mediated secretion gene therapy. | neovascularisation (nv) within the eye often results in visual loss. vascular endothelial growth factor (vegf) has been implicated in the development of ocular nv. previous studies have shown that vegf antagonists successfully suppressed retinal and choroidal nv in animal models. however, the systemic approach and transient nature of the delivery systems used in these studies hinder therapeutic application. to achieve stable and localised ocular anti-angiogenic therapy, we explored the use of re ... | 2002 | 12040462 |
| obstacles to human hematopoietic stem cell transduction by recombinant adeno-associated virus 2 vectors. | recombinant adeno-associated virus 2 (aav) vectors have proven to be a potentially useful alternative to the more commonly used retroviral and adenoviral vectors for gene therapy in humans. their safety and efficacy in phase i clinical trials for gene therapy of cystic fibrosis and hemophilia b have been well documented, and their remarkable versatility and efficacy in a wide variety of pre-clinical models of human diseases have catapulted these vectors to the forefront. aav vectors have been sh ... | 2002 | 12046848 |
| current issues in cochlear gene transfer. | cochlear gene therapy represents a potential experimental and therapeutic tool to understand and treat deafness. in designing cochlear gene transfer studies, the chosen route of delivery of vector and the choice of gene therapy vector have to be given careful consideration. several different routes of delivery have been tested in our laboratory including infusion with osmotic minipump, direct microinjection into the cochlea and application of vector-transgene complex-soaked gelfoam((r)) into the ... | 2002 | 12053135 |
| viral-mediated gene transfer to study the molecular physiology of the mammalian inner ear. | several classes of viral vectors including adenovirus, adeno-associated virus, herpes simplex virus, lentivirus and vaccinia virus have been reported to infect cells of the inner ears of mammals and may be useful for protein manipulation and therapeutic purposes. we have screened a few of these for use as vectors to mediate gene transfer into the sensory hair cells of organotypic cultures from the neonatal mouse cochlea and utricle. recombinant, replication-deficient adenovirus has emerged as a ... | 2002 | 12053137 |
| micro-dystrophin cdna ameliorates dystrophic phenotypes when introduced into mdx mice as a transgene. | the adeno-associated virus vector is a good tool for gene transfer into skeletal muscle, but the length of a gene that can be incorporated is limited. to develop a gene therapy for duchenne muscular dystrophy, we generated a series of rod-truncated micro-dystrophin cdnas: m3 (one rod repeat, 3.9 kb), ax11 (three rod repeats, 4.4 kb), and cs1 (four rod repeats, 4.9 kb). these micro-dystrophins, driven by a cag promoter, were used to produce transgenic (tg) mdx mice and all three micro-dystrophins ... | 2002 | 12054513 |
| [progress in somatic gene therapy of retinal degeneration in the animal model]. | more than 60 genes responsible for human retinal dystrophies have already been identified. most of them are either expressed in the photoreceptor or in the retinal pigment epithelium (rpe). therefore these cells have become the target of new therapeutical strategies on a molecular level. the most promising approach at present is somatic gene therapy, which has been developed over the last years and the principle has now been established in animal models. for gene therapy of inherited retinal deg ... | 2002 | 12058500 |
| adeno-associated virus dna in human gestational trophoblastic disease. | previous studies had shown a correlation between infection with the human adeno-associated virus (aav) and spontaneous abortion in early pregnancy. furthermore, aav dna had been detected in cells of the human trophoblast lines, jeg-3, jar, and bewo, in cells of the human amnion line, fl, and in trophoblasts from amnion fluids. infectious aav virions could be isolated from amnion fluids. to further analyse aav infection during pregnancy, we tested material from gestational trophoblastic disease f ... | 2002 | 12061857 |
| analysis of adeno-associated virus-mediated ex vivo transferred human beta-globin gene in bone marrow engrafted mice. | adeno-associated virus (aav)-2 was developed as a useful vector for human gene therapy. in this report, we analyzed the integration and expression of aav-mediated ex vivo transferred human beta-globin gene in bone marrow (bm) reconstituted mice. recombinant aav (raav) containing human beta-globin gene was packaged by infecting individual g418-resistant bhk-21 cell clones integrated with the plasmid av53hs432deltabeta2.0neo with recombinant herpes simplex virus, which can express rep and cap gene ... | 2002 | 12065900 |
| herpes simplex virus type 1/adeno-associated virus rep(+) hybrid amplicon vector improves the stability of transgene expression in human cells by site-specific integration. | herpes simplex virus type 1 (hsv-1) amplicon vectors are promising gene delivery tools, but their utility in gene therapy has been impeded to some extent by their inability to achieve stable transgene expression. in this study, we examined the possibility of improving transduction stability in cultured human cells via site-specific genomic integration mediated by adeno-associated virus (aav) rep and inverted terminal repeats (itrs). a rep(-) hsv/aav hybrid amplicon vector was made by inserting a ... | 2002 | 12072515 |
| herpes simplex virus type 1/adeno-associated virus hybrid vectors mediate site-specific integration at the adeno-associated virus preintegration site, aavs1, on human chromosome 19. | herpes simplex virus type 1 (hsv-1)-based amplicon vectors have a large transgene capacity and can efficiently infect many different cell types. one disadvantage of hsv-1 vectors is their instability of transgene expression. by contrast, vectors based on adeno-associated virus (aav) can either persist in an episomal form or integrate into the host cell genome, thereby supporting long-term gene expression. aav expresses four rep genes, rep68, -78, -40, and -52. of those, rep68 or rep78 are suffic ... | 2002 | 12072516 |
| adeno-associated virus type-2 expression of pigmented epithelium-derived factor or kringles 1-3 of angiostatin reduce retinal neovascularization. | neovascular diseases of the retina include age-related macular degeneration and diabetic retinopathy, and together they comprise the leading causes of adult-onset blindness in developed countries. current surgical, pharmaceutical, and laser therapies for age-related macular degeneration (amd) rarely result in improved vision, do not significantly prevent neovascularization (nv), and often result in at least some vision loss. to address this therapeutic gap, we determined the efficacy of recombin ... | 2002 | 12072560 |
| adeno-associated viral delivery of gdnf promotes recovery of dopaminergic phenotype following a unilateral 6-hydroxydopamine lesion. | glial cell line-derived neurotrophic factor (gdnf) is a potent neurotrophic factor for dopamine neurons that has been proposed for use in the treatment of parkinson's disease (pd). previous studies using viral vectors to deliver gdnf in rodent models of pd have entailed administering the virus either prior to or immediately after neurotoxin-induced lesions, when the nigrostriatal pathway is largely intact, a paradigm that does not accurately reflect the clinical situation encountered with parkin ... | 2002 | 12075987 |
| adeno-associated virus (aav)-mediated gene transfer in respiratory epithelium and submucosal gland cells in human fetal tracheal organ culture. | since the discovery of the cystic fibrosis transmembrane regulator (cftr) gene, cystic fibrosis has been an attractive target for gene therapy. postnatal gene transfer in the respiratory epithelium has been difficult and particularly inefficient in the submucosal gland cells, the target cells for cftr gene transfer. the authors hypothesized that during development, there is a favorable environment for fetal gene therapy with fewer physical barriers to efficient gene transfer and more accessible ... | 2002 | 12077770 |
| temporal acceleration of the human papillomavirus life cycle by adeno-associated virus (aav) type 2 superinfection in natural host tissue. | epidemiologically, certain human papillomaviruses are positively associated with cervical cancer, while adeno-associated viruses (aav-2) are negatively associated with this same cancer. both hpv and aav productively replicate in differentiating keratinocytes of the skin and interact with each other. however, aav has a relatively fast life cycle, generating infectious progeny by the third to fourth day of an organotypic epithelial raft culture. in contrast, hpv is slow, generating infectious prog ... | 2002 | 12083819 |
| hyper-phosphorylation of the adeno-associated virus rep78 protein inhibits terminal repeat binding and helicase activity. | the replication (rep) proteins of adeno-associated virus (aav) play prominent roles in regulation of viral dna replication, rna transcription, assembly of an infectious virion and establishment of the provirus. we have previously demonstrated that all four rep proteins are phosphorylated on serine residues [virology 23 (1997) 332-336]. reversible phosphorylation may provide a mechanism for regulating rep protein function. to test this hypothesis, we used the phosphatase inhibitor okadaic acid (o ... | 2002 | 12084576 |
| humoral immune response to recombinant adenovirus and adeno-associated virus after in utero administration of viral vectors in mice. | adenovirus and adeno-associated virus vector-mediated gene delivery is limited by the induction of a humoral immune response that prevents readministration. to determine whether viral delivery in the "preimmune" fetus would produce dose- or time-dependent tolerance, we evaluated the humoral immune response after sequential pre- and postnatal virus administration. we evaluated six injection route and viral dose combinations of adenovirus (intra-amniotic, intrahepatic, and intramuscular injection ... | 2002 | 12084854 |
| adenoviral vegf-c overexpression induces blood vessel enlargement, tortuosity, and leakiness but no sprouting angiogenesis in the skin or mucous membranes. | vascular endothelial growth factors (vegfs) and their receptors (vegfrs) are important regulators of blood and lymphatic vessel growth and vascular permeability. the vegf-c/vegfr-3 signaling pathway is crucial for lymphangiogenesis, and heterozygous inactivating missense mutations of the vegfr-3 gene are associated with hereditary lymphedema. however, vegf-c can have potent effects on blood vessels because its receptor vegfr-3 is expressed in certain blood vessels and because the fully processed ... | 2002 | 12087065 |
| efficient mouse airway transduction following recombination between aav vectors carrying parts of a larger gene. | the small packaging capacity of adeno-associated virus (aav) vectors limits the utility of this promising vector system for transfer of large genes. we explored the possibility that larger genes could be reconstituted following homologous recombination between aav vectors carrying overlapping gene fragments. an alkaline phosphatase (ap) gene was split between two such aav vectors (rec vectors) and packaged using aav2 or aav6 capsid proteins. rec vectors having either capsid protein recombined to ... | 2002 | 12089554 |
| targeted transgene insertion into human chromosomes by adeno-associated virus vectors. | efficient methods are needed for the precise genetic manipulation of diploid human cells, in which cellular senescence and low conventional gene targeting rates limit experimental and therapeutic options. we have shown previously that linear, single-stranded dna vectors based on adeno-associated virus (aav) could accurately introduce small (<20 bp) genetic modifications into homologous human chromosomal sequences. here we have used aav vectors to introduce large (>1 kb) functional transgene cass ... | 2002 | 12089561 |
| dose and promoter effects of adeno-associated viral vector for green fluorescent protein expression in the rat brain. | previous studies demonstrated that the rat neuron-specific enolase (nse) promoter is effective for transgene expression in the brain in a variety of adeno-associated virus-2 vectors. this study evaluated the dose response and longer time course of this promoter and compared it to two cytomegalovirus/chicken beta-actin hybrid (cba) promoter-based systems. nse promoter-driven green fluorescent protein (gfp)-expressing neurons were found at doses as low as 10(7) particles, with expression increasin ... | 2002 | 12093083 |
| an adenoviral expression system for aav rep78 using homologous recombination. | the construction and amplification of adenoviral (ad) vectors expressing biologically active transgenes that are cytotoxic or inhibit ad replication can be extremely difficult, if not impossible. in this study, we harnessed the ability of ad genomes to undergo efficient homologous recombination to reconstitute the adeno-associated virus (aav) rep78 gene, a cytotoxic gene that strongly inhibits ad replication, which was divided between two parental, first-generation ad vectors. a functional open ... | 2002 | 12095308 |
| improved method of recombinant aav2 delivery for systemic targeted gene therapy. | a major hurdle in most current gene therapy modalities is the ability to transduce target tissues at very high efficiencies that ultimately lead to therapeutic levels of transgene expression. we have developed a novel method of recombinant adeno-associated virus 2 (raav) delivery that results in increased vector transduction efficiencies using microspheres reversibly conjugated to raav vectors. we hypothesize that conjugation to microspheres should result in a higher effective concentration of v ... | 2002 | 12095310 |
| kinetics and frequency of adeno-associated virus site-specific integration into human chromosome 19 monitored by quantitative real-time pcr. | adeno-associated virus type 2 (aav-2) integrates specifically into a site on human chromosome 19 (chr-19) called aavs1. to study the kinetics and frequency of chr-19-specific integration after aav infection, we developed a rapid, sensitive, and quantitative real-time pcr assay for aav inverted terminal repeat-chr-19-specific junctions. despite the known variability of junction sites, conditions were established that ensured reliable quantification of integration rates within hours after aav infe ... | 2002 | 12097568 |
| virus-mediated transduction of murine retina with adeno-associated virus: effects of viral capsid and genome size. | gene therapy vectors based on adeno-associated viruses (aavs) show promise for the treatment of retinal degenerative diseases. in prior work, subretinal injections of aav2, aav5, and aav2 pseudotyped with aav5 capsids (aav2/5) showed variable retinal pigmented epithelium (rpe) and photoreceptor cell transduction, while aav2/1 predominantly transduced the rpe. to more thoroughly compare the efficiencies of gene transfer of aav2, aav3, aav5, and aav6, we quantified, using stereological methods, th ... | 2002 | 12097579 |
| delivery of glucose-6-phosphatase in a canine model for glycogen storage disease, type ia, with adeno-associated virus (aav) vectors. | therapy in glycogen storage disease type ia (gsd ia), an inherited disorder of carbohydrate metabolism, relies on nutritional support that postpones but fails to prevent long-term complications of gsd ia. in the canine model for gsd ia, we evaluated the potential of intravenously delivered adeno-associated virus (aav) vectors for gene therapy. in three affected canines, liver glycogen was reduced following hepatic expression of canine glucose-6-phosphatase (g6pase). two months after aav vector a ... | 2002 | 12101432 |
| recombinant adeno-associated virus type 2 mediates highly efficient gene transfer in regenerating rat skeletal muscle. | the recent identification of genes responsible for several muscle diseases, particularly inherited myopathies, has made gene transfer to pathologic muscle tissue an attractive research field. as early pathologic changes in myopathic muscle involve repeated necrosis-regeneration cycles, leading to the coexistence of myofibers at different stages of maturity, a delivery system for efficient, durable gene therapy of inherited muscle diseases should allow gene transfer into myofibers at any stage of ... | 2002 | 12101435 |
| rescue of hereditary form of dilated cardiomyopathy by raav-mediated somatic gene therapy: amelioration of morphological findings, sarcolemmal permeability, cardiac performances, and the prognosis of to-2 hamsters. | the hereditary form comprises approximately 1/5 of patients with dilated cardiomyopathy (dcm) and is a major cause of advanced heart failure. medical and socioeconomic settings require novel treatments other than cardiac transplantation. to-2 strain hamsters with congenital dcm show similar clinical and genetic backgrounds to human cases that have defects in the delta-sarcoglycan (delta-sg) gene. to examine the long-term in vivo supplement of normal delta-sg gene driven by cytomegalovirus promot ... | 2002 | 11805334 |
| enhancement of cisplatin-induced apoptosis by infection with adeno-associated virus type 2. | the non-pathogenic human adeno-associated virus, aav, has been shown to sensitize human cancer cells and experimental tumors towards the action of chemotherapeutic agents such as cisplatin. since chemotherapeutic drugs mainly involve the induction of apoptosis, we investigated whether 1 possible mechanism of aav-mediated sensitization of human tumor cells may result from an enhancement of cisplatin-induced apoptosis. in hela and a549 cells, infection with aav type 2 (aav-2) increased cisplatin-i ... | 2002 | 11807802 |
| recombinant adeno-associated virus serotype 2 vectors mediate stable interleukin 10 secretion from salivary glands into the bloodstream. | we have constructed a recombinant adeno-associated virus serotype 2 vector encoding human interleukin 10 (raavhil10). il-10 is a potent antiinflammatory/immune cytokine, which has received growing attention for its therapeutic potential. human il-10 (hil-10) production was virus dose dependent after in vitro infection of hsg cells, a human submandibular gland cell line. the vector-derived hil-10 produced was biologically active, as the medium from raavhil10-infected hsg cells caused a dose-depen ... | 2002 | 11812284 |
| gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene. | ischemia and oxidative stress are the leading mechanisms for tissue injury. an ideal strategy for preventive/protective therapy would be to develop an approach that could confer long-term transgene expression and, consequently, tissue protection from repeated ischemia/reperfusion injury with a single administration of a therapeutic gene. in the present study, we used recombinant adeno-associated virus (raav) as a vector for direct delivery of the cytoprotective gene heme oxygenase-1 (ho-1) into ... | 2002 | 11827926 |
| a deviant immune response to viral proteins and transgene product is generated on subretinal administration of adenovirus and adeno-associated virus. | the immune response after ocular exposure to foreign antigens varies substantially from that of a typical systemic response. anterior chamber associated immune deviation (acaid) has been well documented. the immune response of the subretinal space has not been studied in as much detail. here, we characterized the immune response of the subretinal space when it encounters the antigens adv-gfp and aav-gfp (recombinant adenovirus or adeno-associated virus, respectively), each delivering the reporte ... | 2002 | 11829519 |