Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
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| adeno-associated virus pseudotype 5 vector improves gene transfer in arthritic joints. | the potential for gene delivery to joints, using recombinant adeno-associated virus (raav) vectors for the treatment of rheumatoid arthritis (ra), has received much attention. different serotypes have different virion shell proteins and, as a consequence, vary in their tropism for diverse tissues. the aim of this study was to compare the transduction efficiency of different aav serotypes encoding murine secreted alkaline phosphatase (mseap) or escherichia coli beta-galactosidase for intraarticul ... | 2005 | 15871674 |
| gene targeting by adeno-associated virus vectors is cell-cycle dependent. | adeno-associated virus (aav) vectors can be used to introduce site-specific mutations into homologous chromosomal sequences. there are many potential applications of this technique, but the process of aav-mediated gene targeting and factors that influence targeting efficiency are not completely understood. we investigated the dependence of aav-mediated gene targeting on the host cell-cycle status. the frequency of gene targeting by aav vectors was compared in dividing and serum-arrested normal h ... | 2005 | 15871683 |
| development and evaluation of the specificity of a cathepsin d proximal promoter in the eye. | recombinant adeno-associated virus (raav)-mediated gene delivery has emerged as a valuable tool for alternative treatment of ocular diseases. cellular specificity of transgene expression could be influenced by either the viral capsid or the choice of promoter. the use of cellular promoter, cathepsin d (catd) proximal promoter, and its potential for application in raav-based gene therapy are evaluated in this study. | 2005 | 15875365 |
| efficacy of an adeno-associated virus 8-pseudotyped vector in glycogen storage disease type ii. | glycogen storage disease type ii (gsd-ii; pompe disease) causes death in infancy from cardiorespiratory failure. the underlying deficiency of acid alpha-glucosidase (gaa; acid maltase) can be corrected by liver-targeted gene therapy in gsd-ii, if secretion of gaa is accompanied by receptor-mediated uptake in cardiac and skeletal muscle. an adeno-associated virus (aav) vector encoding human (h) gaa was pseudotyped as aav8 (aav2/8) and injected intravenously into immunodeficient gsd-ii mice. high ... | 2005 | 15585406 |
| hsp70 gene transfer by adeno-associated virus inhibits mptp-induced nigrostriatal degeneration in the mouse model of parkinson disease. | mitochondrial dysfunction and oxidative stress have been implicated in parkinson disease (pd). in addition, genetic evidence points to an important role of protein misfolding, aggregation, and failure in the proteasomal degradation of specific neuronal proteins in the pathogenesis of pd. the chaperone heat-shock protein 70 (hsp70) reduces protein misfolding and aggregation and protects cells against a variety of adverse conditions, including oxidative stress. moreover, hsp70 exerts antiapoptotic ... | 2005 | 15585408 |
| efficient gene transfer of cd40 ligand into ovarian carcinoma cells with a recombinant adeno-associated virus vector. | recombinant adeno-associated virus type 2 (raav) has many properties of an ideal vector for gene therapy: broad spectrum of susceptible cells, efficient gene transfer, persistent transgene expression in vivo, and no indiction of vector-related toxicity. ovarian carcinoma cell lines, however, were previously reported to be quite resistant to raav transduction. using an optimized adenovirus-free packaging system, highly purified raav vectors coding for the enhanced green fluorescent protein (aav/e ... | 2005 | 15586229 |
| promoters and serotypes: targeting of adeno-associated virus vectors for gene transfer in the rat central nervous system in vitro and in vivo. | the brain parenchyma consists of several different cell types, such as neurones, astrocytes, microglia, oligodendroglia and epithelial cells, which are morphologically and functionally intermingled in highly complex three-dimensional structures. these different cell types are also present in cultures of brain cells prepared to serve as model systems of cns physiology. gene transfer, either in a therapeutic attempt or in basic research, is a fascinating and promising tool to manipulate both the c ... | 2005 | 15542619 |
| a realistic chance for gene therapy in the near future. | the expanding knowledge of the genetic and cellular mechanisms of human diseases in the post-genomic era coupled with the development of different vector systems to efficiently transfer genes to a variety of cell types and organs in vivo gave rise to the concept of gene therapy as a promising therapeutic option for genetic and acquired diseases. gene therapy has been the focus of both enthusiasm and critique in the past years. major progress has been achieved in evaluating gene therapy in clinic ... | 2005 | 15549408 |
| adeno-associated virus-mediated delivery of a mutant endostatin suppresses ovarian carcinoma growth in mice. | earlier studies have shown that a point mutation in human endostatin at position 125 (human endostatin wherein proline 125 was substituted with alanine, p125a-endostatin) improves endothelial cell binding and antiangiogenic activity. in the present study, we investigated the effect of recombinant adeno-associated virus (raav)-mediated gene delivery of p125a-endostatin (raav-p125aendo) in a mouse model of ovarian carcinoma. intramuscular (i.m.) injection of raav-p125aendo resulted in a dose-depen ... | 2005 | 15550927 |
| myocardial gene transfer and long-term expression following intracoronary delivery of adeno-associated virus. | adeno-associated viral vectors (aav) can direct long-term gene expression in post-mitotic cells. previous studies have established that long-term cardiac gene transfer results from intramuscular injection into the heart. cardiac gene transfer after direct intracoronary delivery of aav in vivo, however, has been minimal in degree, and indirect intracoronary delivery, an approach used in an increasing number of studies, appears to be receiving more attention. to determine the utility of indirect i ... | 2005 | 15515115 |
| immune responses following salivary gland administration of recombinant adeno-associated virus serotype 2 vectors. | gene transfer to salivary glands (sgs) can be accomplished in a minimally invasive manner, resulting in stable, long-term secretion of the transgene product. therefore, sgs provide a novel target site for several potentially useful clinical gene therapeutics applications. previous studies have indicated that intravenous, intramuscular and intranasal administration of recombinant adeno-associated virus serotype 2 (raav2) vectors induce host immune responses. there are no reported studies on immun ... | 2005 | 15515118 |
| gene transfer into skeletal muscle using novel aav serotypes. | skeletal muscle is an interesting target for gene delivery because of its mass and because the vectors can be delivered in a noninvasive way. adeno-associated virus (aav) vectors are capable of transducing skeletal muscle fibers and achieving stable and safe transgene expression. to date, most animal experiments using aav have been based on aav serotype 2, but some recent studies have demonstrated that aav1 is more efficient than aav2/2 in transducing muscle fibers. recently, novel aavs (aav7 an ... | 2005 | 15517544 |
| transfer of the full-length dystrophin-coding sequence into muscle cells by a dual high-capacity hybrid viral vector with site-specific integration ability. | duchenne muscular dystrophy (dmd) is caused by mutations in the dmd gene, making it a potential target for gene therapy. there is, however, a scarcity of vectors that can accommodate the 14-kb dmd cdna and permanently genetically correct muscle tissue in vivo or proliferating myogenic progenitors in vitro for use in autologous transplantation. here, a dual high-capacity adenovirus-adeno-associated virus (hcad/aav) vector with two full-length human dystrophin-coding sequences flanked by aav integ ... | 2005 | 15709034 |
| recombinant adeno-associated virus 2-mediated antiangiogenic prevention in a mouse model of intraperitoneal ovarian cancer. | in the present study, we sought to determine the potential of sustained transgene expression by a single i.m. administration of recombinant adeno-associated virus 2 (raav) encoding angiostatin and endostatin in inhibiting i.p. ovarian cancer growth and dissemination in a preclinical mouse model. | 2005 | 15709207 |
| gene therapy of metachromatic leukodystrophy. | metachromatic leukodystrophy (mld) is a lysosomal storage disease that is caused by a deficiency of arylsulfatase a (asa). the deficiency results in the intralysosomal accumulation of the acidic sphingolipid 3-o-sulfogalactosyl-ceramide (sulfatide). patients suffer from progressive demyelination and die from multiple neurological deficits. curative treatment is not available. asa bears mannose 6-phosphate residues which function as recognition markers in endosome/lysosome-specific targeting path ... | 2005 | 15709909 |
| anti-angiogenic therapy subsequent to adeno-associated-virus-mediated immunotherapy eradicates lymphomas that disseminate to the liver. | liver cancer has a very poor prognosis and lacks effective therapy. we have previously demonstrated that intraportal injection of adeno-associated-viral (aav) particles that express angiostatin lead to long-term expression of angiostatin capable of suppressing the outgrowth of el-4 tumors in the liver. here we combine aav-mediated angiostatin therapy with immunotherapy by employing an aav vector encoding the t-cell costimulator b7.1. incubation of el-4 cells with aav-b7.1 viruses resulted in the ... | 2005 | 15472906 |
| stable secondary structure near the nicking site for adeno-associated virus type 2 rep proteins on human chromosome 19. | adeno-associated virus serotype 2 (aav-2) can preferentially integrate its dna into a 4-kb region of human chromosome 19, designated aavs1. the nicking activity of aav-2's rep68 or rep78 proteins is essential for preferential integration. these proteins nick at the viral origin of dna replication and at a similar site within aavs1. the current nicking model suggests that the strand containing the nicking site is separated from its complementary strand prior to nicking. in aav serotypes 1 through ... | 2005 | 15731249 |
| large-scale molecular characterization of adeno-associated virus vector integration in mouse liver. | recombinant adeno-associated virus (raav) vector holds promise for gene therapy. despite a low frequency of chromosomal integration of vector genomes, recent studies have raised concerns about the risk of raav integration because integration occurs preferentially in genes and accompanies chromosomal deletions, which may lead to loss-of-function insertional mutagenesis. here, by analyzing 347 raav integrations in mice, we elucidate novel features of raav integration: the presence of hot spots for ... | 2005 | 15731255 |
| regional intravascular delivery of aav-2-f.ix to skeletal muscle achieves long-term correction of hemophilia b in a large animal model. | in earlier work, we showed that adeno-associated virus-mediated delivery of a factor ix gene to skeletal muscle by direct intramuscular injection resulted in therapeutic levels of circulating factor ix in mice. however, achievement of target doses in humans proved impractical because of the large number of injections required. we used a novel intravascular delivery technique to achieve successful transduction of extensive areas of skeletal muscle in a large animal with hemophilia. we provide her ... | 2005 | 15479726 |
| adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart. | systemic gene delivery into muscle has been a major challenge for muscular dystrophy gene therapy, with capillary blood vessels posing the principle barrier and limiting vector dissemination. previous efforts to deliver genes into multiple muscles have relied on isolated vessel perfusion or pharmacological interventions to enforce broad vector distribution. we compared the efficiency of multiple adeno-associated virus (aav) vectors after a single injection via intraperitoneal or intravenous rout ... | 2005 | 15735640 |
| valproic acid enhances gene expression from viral gene transfer vectors. | viral vectors represent an efficient delivery method for in vitro and in vivo gene transfer, and their utility may be further enhanced through the use of pharmacologic agents that increase gene expression. here, we demonstrate that valproic acid (vpa), a drug which is widely used for the treatment of epilepsy and mood disorders, enhances and prolongs expression of exogenous genes in cells transduced with various gene transfer agents, including adenovirus, adeno-associated virus and herpesvirus v ... | 2005 | 15737413 |
| the adeno associated viral vector as a strategy for intradiscal gene transfer in immune competent and pre-exposed rabbits. | experimental animal study. | 2005 | 15738780 |
| overexpression of soluble trail induces apoptosis in human lung adenocarcinoma and inhibits growth of tumor xenografts in nude mice. | recombinant adeno-associated virus 2/5 (raav2/5), a hybrid raav-2 with aav-5 capsid, seems to be a very efficient delivery vector for the transduction of the lung adenocarcinoma cell line a549. infection of the a549 cell line with a raav2/5 vector encoding the extracellular domain of tumor necrosis factor-related apoptosis-inducing ligand (trail, amino acids 114-281) resulted in secretion of soluble trail (strail) and induction of apoptosis in these cells. raav2/5-strail mediated delivery and st ... | 2005 | 15753363 |
| adeno-associated virus-mediated gene transfer of the heart/muscle adenine nucleotide translocator (ant) in mouse. | mitochondrial myopathy, associated with muscle weakness and progressive external ophthalmoplegia, is caused by mutations in mitochondria oxidative phosphorylation genes including the heart-muscle isoform of the mitochondrial adenine nucleotide translocator (ant1). to develop therapies for mitochondrial disease, we have prepared a recombinant adeno-associated viral vector (raav) carrying the mouse ant1 cdna. this vector has been used to transduce muscle cells and muscle from ant1 mutant mice, whi ... | 2005 | 15647764 |
| stable inhibition of hepatitis b virus proteins by small interfering rna expressed from viral vectors. | there has been much research into the use of rna interference (rnai) for the treatment of human diseases. many viruses, including hepatitis b virus (hbv), are susceptible to inhibition by this mechanism. however, for rnai to be effective therapeutically, a suitable delivery system is required. | 2005 | 15756649 |
| improved neuronal transgene expression from an aav-2 vector with a hybrid cmv enhancer/pdgf-beta promoter. | adeno-associated virus type 2 (aav-2) vectors are highly promising tools for gene therapy of neurological disorders. after accommodating a cellular promoter, aav-2 vectors are able to drive sustained expression of transgene in the brain. this study aimed to develop aav-2 vectors that also facilitate a high level of neuronal expression by enhancing the strength of a neuron-specific promoter, the human platelet-derived growth factor beta-chain (pdgf) promoter. | 2005 | 15756650 |
| [effects of cd151 on migration of human tongue squamous carcinoma cell line tca8113]. | over-expression of cd151 gene in tumor tissues may be associated with metastasis and poor prognosis of cancer, but the mechanism is unknown. this study was designed to determine the effects of cd151 gene on migration of human tongue squamous carcinoma cell line tca8113. | 2005 | 15757524 |
| [construction of an adeno-associated virus vector expressing ctla-4ig and its expression in the transplanted liver allografts]. | to construct a recombinant adeno-associated virus vector psnav expressing ctla-4ig and to demonstrate its expression in transplanted liver allografts and to see if a long term inhibitive effect of ctla-4ig could be obtained though its use. | 2005 | 15760550 |
| [binding and inhibition of adeno-associated virus rep78 protein with hepatitis b virus c promoter]. | adeno-associated virus (aav) rep78 is known for its inhibitory effects on replication of several viruses and oncogenes transformations. the study was to investigate the effect of rep78 on hepatitis b virus c (hbv-c) gene and the mechanism of it. | 2005 | 15760551 |
| long-term inducible gene expression in the eye via adeno-associated virus gene transfer in nonhuman primates. | adeno-associated viral gene therapy has shown promise for the treatment of inherited and degenerative diseases in a variety of animal models. some of the most dramatic results have been obtained in the field of ocular gene therapy, where efficacy has been tremendous in inherited and acquired retinal disorders. for the promise of this approach to be realized it will be necessary to create vectors capable of pharmacologic or physiologic regulation of the transgene. we describe in this paper a dime ... | 2005 | 15761258 |
| efficient transduction of vascular endothelial cells with recombinant adeno-associated virus serotype 1 and 5 vectors. | recombinant adeno-associated virus (raav) has become an attractive tool for gene therapy because of its ability to transduce both dividing and nondividing cells, elicit a limited immune response, and the capacity for imparting long-term transgene expression. previous studies have utilized raav serotype 2 predominantly and found that transduction of vascular cells is relatively inefficient. the purpose of the present study was to evaluate the transduction efficiency of raav serotypes 1 through 5 ... | 2005 | 15761263 |
| co-vaccination with adeno-associated virus vectors encoding human papillomavirus 16 l1 proteins and adenovirus encoding murine gm-csf can elicit strong and prolonged neutralizing antibody. | non-infectious human papillomavirus-like particles (vlps), encoded by the major capsid gene l1, have been shown to be effective as vaccines to prevent cervical cancer. we have developed the genetic immunization of the l1 gene to induce a neutralizing antibody. we constructed and generated a recombinant adeno-associated virus encoding human papillomavirus (hpv) 16 l1 protein that could form virus-like particles in transduced cells. previous reports have demonstrated that the formation of vlp is n ... | 2005 | 15386434 |
| repair of articular cartilage defect by autologous transplantation of basic fibroblast growth factor gene-transduced chondrocytes with adeno-associated virus vector. | to examine the effects of basic fibroblast growth factor (bfgf) gene-transduced chondrocytes on the repair of articular cartilage defects. | 2005 | 15641065 |
| [influences of recombinant adeno-associated virus-mediated decorin gene transfection on cell cycle and apoptosis of siha cells]. | decorin (dcn), a multi-efficiency factor, has many important functions, such as influencing fibril stability, and interacting with extracellular matrix molecules to influence cell adhesion. this study was to investigate influences of dcn on cell cycle and apoptosis of siha cells via recombinant adeno-associated virus-mediated dcn gene (raav.dcn) transfection. | 2005 | 15642196 |
| adeno-associated virus vectors for short hairpin rna expression. | five recent publications have documented the successful development and use of gene transfer vectors based on adeno-associated virus (aav) for expressing short hairpin rna (shrna). in cultured mammalian cells and in whole animals, infection with these vectors was shown to result in specific, efficient, and stable knockdown of various targeted endo- or exogenous genes. here we review this exciting approach, to trigger rna interference in vitro and in vivo by shrna expressed from aav vectors, and ... | 2005 | 15644194 |
| viral transport of dna damage that mimics a stalled replication fork. | adeno-associated virus type 2 (aav2) infection incites cells to arrest with 4n dna content or die if the p53 pathway is defective. this arrest depends on aav2 dna, which is single stranded with inverted terminal repeats that serve as primers during viral dna replication. here, we show that aav2 dna triggers damage signaling that resembles the response to an aberrant cellular dna replication fork. uv treatment of aav2 enhances the g2 arrest by generating intrastrand dna cross-links which persist ... | 2005 | 15596849 |
| hepatocyte growth factor receptor is a coreceptor for adeno-associated virus type 2 infection. | after the first attachment of virus to the cell surface through a primary receptor, efficient entry of virus requires the presence of a coreceptor. for adeno-associated virus type 2 (aav2) infection, heparan sulfate proteoglycan is supposed as the primary receptor, and alphavbeta5 integrin and fgfr1 are reported to act as coreceptors. in this study, we were able to demonstrate that hepatocyte growth factor receptor, c-met, is also a coreceptor for aav2 infection. aav2-mediated transgene analyses ... | 2005 | 15596854 |
| identification of an adeno-associated virus rep protein binding site in the adenovirus e2a promoter. | adeno-associated virus (aav) and other parvoviruses inhibit proliferation of nonpermissive cells. the mechanism of this inhibition is not thoroughly understood. to learn how aav interacts with host cells, we investigated aav's interaction with adenovirus (ad), aav's most efficient helper virus. coinfection with ad and aav results in an aav-mediated inhibition of ad5 gene expression and replication. the aav replication proteins (rep) activate and repress gene expression from aav and heterologous ... | 2005 | 15596798 |
| distribution of aav2-haadc-transduced cells after 3 years in parkinsonian monkeys. | the present report describes for the first time, the stability of recombinant adeno-associated virus serotype 2 (aav2) human aromatic l-amino acid decarboxylase (haadc) gene transfer after 3-year survival time in a non-human primate model of parkinson's disease. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys were treated with six injections of 30 microl/site of aav2-haadc at a concentration of 2 x 10(12) vg/ml into the caudate and putamen. stereological analysis revealed a 46.6% i ... | 2006 | 16407771 |
| adeno-associated virus types 5 and 6 use distinct receptors for cell entry. | the transduction efficiency of adeno-associated virus (aav) vectors in various somatic tissues is determined primarily by the viral capsid proteins. in contrast to vectors made with aav type 2 capsids, those having type 5 or 6 capsids show high transduction rates in airway epithelial cells, in a range that should be sufficient for treating lung disease. here we have compared the properties of vectors made with aav5 or aav6 capsid proteins to determine whether their receptor usage is similar, and ... | 2006 | 16409121 |
| adeno-associated virus-mediated gene transfer of a secreted form of trail inhibits tumor growth and occurrence in an experimental tumor model. | tumor necrosis factor-related apoptosis-inducing ligand (trail) induces cell death in various tumor cells, but relatively spares normal cells. recombinant adeno-associated virus (raav) vectors have a number of advantages including in vivo long-term gene expression. here, we assessed the biological activity of a novel, secreted form of trail (strail) for cancer gene therapy using a raav2 vector. | 2006 | 16144019 |
| gene therapy strategies for duchenne muscular dystrophy utilizing recombinant adeno-associated virus vectors. | gene transfer vectors based on adeno-associated virus (aav) are now widely used in the field of gene therapy. these vectors have been studied for their potential use in treating many diseases, among them the muscular dystrophies, the most common of which is duchenne muscular dystrophy (dmd). several recent advances in the areas of aav serotype analysis, transgene engineering, and vector delivery to muscle, together with novel means of rescuing mutant mrna transcripts, have yielded impressive res ... | 2006 | 16361117 |
| viral gene therapy strategies: from basic science to clinical application. | a major impediment to the successful application of gene therapy for the treatment of a range of diseases is not a paucity of therapeutic genes, but the lack of an efficient non-toxic gene delivery system. having evolved to deliver their genes to target cells, viruses are currently the most effective means of gene delivery and can be manipulated to express therapeutic genes or to replicate specifically in certain cells. gene therapy is being developed for a range of diseases including inherited ... | 2006 | 16362990 |
| phenotype correction of hemophilia a mice with adeno-associated virus vectors carrying the b domain-deleted canine factor viii gene. | adeno-associated virus (aav) vectors carrying the b domain-deleted canine fviii (bdd cfviii) gene utilizing the beta-actin minimum promoter (167b) pseudotyped with serotype 1 (aav1-beta-actin-cfviii) and serotype 8 (aav8-beta-actin-cfviii) were developed to express cfviii in hemophilia a mice. fviii clotting activities measured by the aptt method increased in hemophilia a mice with intramuscular injection of aav1-beta-actin-cfviii in a dose-dependent manner. therapeutic fviii levels (2.9+/-1.0%) ... | 2006 | 16371232 |
| impact of capsid conformation and rep-capsid interactions on adeno-associated virus type 2 genome packaging. | single-stranded genomes of adeno-associated virus (aav) are packaged into preformed capsids. it has been proposed that packaging is initiated by interaction of genome-bound rep proteins to the capsid, thereby targeting the genome to the portal of encapsidation. here we describe a panel of mutants with amino acid exchanges in the pores at the fivefold axes of symmetry on aav2 capsids with reduced packaging and reduced rep-capsid interaction. mutation of two threonines at the rim of the fivefold p ... | 2006 | 16378983 |
| mutations on the external surfaces of adeno-associated virus type 2 capsids that affect transduction and neutralization. | mutations were made at 64 positions on the external surface of the adeno-associated virus type 2 (aav-2) capsid in regions expected to bind antibodies. the 127 mutations included 57 single alanine substitutions, 41 single nonalanine substitutions, 27 multiple mutations, and 2 insertions. mutants were assayed for capsid synthesis, heparin binding, in vitro transduction, and binding and neutralization by murine monoclonal and human polyclonal antibodies. all mutants made capsid proteins within a l ... | 2006 | 16378984 |
| enhanced transduction of mouse salivary glands with aav5-based vectors. | we previously demonstrated that recombinant adeno-associated virus vectors based on serotype 2 (raav2) can direct transgene expression in salivary gland cells in vitro and in vivo. however, it is not known how other raav serotypes perform when infused into salivary glands. the capsids of serotypes 4 and 5 are distinct from raav2 and from each other, suggesting that they may direct binding and entry into different cell types. in the present study, we investigated the tropisms, transduction effici ... | 2006 | 16341060 |
| efficient neuronal gene transfer with aav8 leads to neurotoxic levels of tau or green fluorescent proteins. | adeno-associated virus (aav) serotype 8 appears to be the strongest of the natural serotypes reported to date for gene transfer in liver and muscle. in this study, we evaluated aav8 in the brain by several methods, including biophotonic imaging of green fluorescent protein (gfp). in the adult rat hippocampus, levels of gfp expressed were clearly greater with aav8 than with aav2 or aav5 by western blot and biophotonic imaging and slightly but significantly greater than aav1 by western blot. in th ... | 2006 | 16325474 |
| a novel role of circadian transcription factor dbp in hippocampal plasticity. | in neurons, a variety of extracellular stimuli are capable of inducing transcriptional events that underlie complex processes ranging from learning to disease. the mechanisms linking these long-lasting cellular modifications to behavior remain to be established. here, we show by microarray analysis that hippocampal activation of glucagon-like peptide-1 receptor (glp-1r), which is associated with improved learning and neuroprotection, results in suppression of the transcription factor dbp (albumi ... | 2006 | 16257226 |
| complete correction of hyperphenylalaninemia following liver-directed, recombinant aav2/8 vector-mediated gene therapy in murine phenylketonuria. | novel recombinant adeno-associated virus vectors pseudotyped with serotype 8 capsid (raav2/8) have recently shown exciting promise as effective liver-directed gene transfer reagents. we have produced a novel liver-specific raav2/8 vector expressing the mouse phenylalanine hydroxylase (pah) cdna and have administered this vector to hyperphenylalaninemic pah-deficient pah(enu2) mice, a model of human phenylketonuria (pku). our hypothesis was that this vector would produce sufficient hepatocyte tra ... | 2006 | 16319949 |
| activators of viral gene expression in polarized epithelial monolayers identified by rapid-throughput drug screening. | epithelial polarity and tight junction formation limit the ability of adenovirus, retrovirus and adeno-associated virus (aav) to deliver and express virally encoded genes. using an extended half-life luciferase assay and high-throughput luminometry, we screened 23 000 compounds and natural product extracts as potentiators to overcome this barrier. seven strong activators were discovered (up to several hundred fold above control) and two of these exhibited spectrum of activity in multiple cell ty ... | 2006 | 16307002 |
| gene therapy for patients with rheumatoid arthritis. | gene therapy seeks either to supply a missing or dysfunctional gene or to ensure continuous long-lasting production of a therapeutic protein. rheumatoid arthritis is a candidate for gene therapy, as the mechanisms leading to joint inflammation and destruction have been partly elucidated. nevertheless, several crucial questions need to be addressed. knowledge of the underlying pathophysiological mechanisms is needed to guide selection of the candidate gene. in the light of current data, tnf and i ... | 2006 | 16226478 |
| viral-mediated temporally controlled dopamine production in a rat model of parkinson disease. | regulation of gene expression is necessary to avoid possible adverse effects of gene therapy due to excess synthesis of transgene products. to reduce transgene expression, we developed a viral vector-mediated somatic regulation system using inducible cre recombinase. a recombinant adeno-associated virus (aav) vector expressing cre recombinase fused to a mutated ligand-binding domain of the estrogen receptor alpha (creer(t2)) was delivered along with aav vectors expressing dopamine-synthesizing e ... | 2006 | 16182609 |
| antitumor efficacy of aav-mediated systemic delivery of interferon-beta. | type i interferons (alpha/beta) have significant antitumor activity although their short half-life and systemic side effects have limited their clinical utility. an alternative dosing schedule of continuous, low-level delivery, as is achieved by gene therapy, rather than intermittent, high concentration pulsed-dosing, might avoid the toxicity of interferon while maintaining its antitumor efficacy. we have tested a gene therapy approach in murine tumor models to treat malignancies that have shown ... | 2006 | 16052229 |
| high levels of persistent expression of alpha1-antitrypsin mediated by the nonhuman primate serotype rh.10 adeno-associated virus despite preexisting immunity to common human adeno-associated viruses. | alpha1-antitrypsin (alpha1at) deficiency is a genetic disorder causing emphysema if serum alpha1at levels are <570 microg/ml. we have shown that intrapleural administration of an aav5alpha1at vector yielded persistent therapeutic alpha1at serum levels. since anti-aav2 and -aav5 antibodies prevalent in humans may limit the use of these common serotypes in gene therapy, we screened 25 aav vectors derived from humans and nonhuman primates for alpha1at expression following intrapleural administratio ... | 2006 | 16260185 |
| multiple human papillomavirus genes affect the adeno-associated virus life cycle. | the risk of cervical cancer, one of the most prevalent cancers in the world, is determined by two viruses. human papillomavirus (hpv) is the main risk factor for developing cervical cancer. however, although little known, it is well substantiated that the human parvovirus adeno-associated virus type 2 (aav), and its encoded rep78 protein, interacts with hpv and lowers the risk of cervical cancer. hpv also contributes to aav inhibition by serving as a helper virus for aav and stimulating higher a ... | 2006 | 16203022 |
| effect of human vasoactive intestinal peptide gene transfer in a murine model of sjogren's syndrome. | sjögren's syndrome (ss), an autoimmune exocrinopathy mainly affecting lachrymal and salivary glands, results in ocular and oral dryness (keratoconjunctivitis sicca and xerostomia). the aetiology and pathogenesis are largely unknown; currently, only palliative treatment is available. | 2006 | 15975969 |
| human immunoglobulin inhibits liver transduction by aav vectors at low aav2 neutralizing titers in scid mice. | long-term cures of hemophilia b have been achieved using aav2 delivering the factor ix gene to the liver of adeno-associated virus (aav)-naive hemophilic animals. however, the clinical success of this approach requires overcoming pre-existing aav neutralizing antibodies prevalent in humans. to better define the inhibition of neutralizing antibodies on aav2-mediated liver transduction, we developed an in vivo passive immunity model. scid mice were first reconstituted to a defined neutralizing tit ... | 2006 | 16249376 |
| species-specific differences in mouse and human airway epithelial biology of recombinant adeno-associated virus transduction. | differences in airway epithelial biology between mice and humans have presented challenges to evaluating gene therapies for cystic fibrosis (cf) using murine models. in this context, recombinant adeno-associated virus (raav) type 2 and raav5 vectors have very different transduction efficiencies in human air-liquid interface (ali) airway epithelia (raav2 approximately = raav5) as compared with mouse lung (raav5 >> raav2). it is unclear if these differences are due to species-specific airway biolo ... | 2006 | 16195538 |
| long-term correction of murine glycogen storage disease type ia by recombinant adeno-associated virus-1-mediated gene transfer. | glycogen storage disease type ia (gsd-ia) is caused by a deficiency in glucose-6-phosphatase-alpha (g6pase-alpha), a nine-transmembrane domain, endoplasmic reticulum-associated protein expressed primarily in the liver and kidney. previously, we showed that infusion of an adeno-associated virus (aav) serotype 2 vector carrying murine g6pase-alpha (aav2-g6pase-alpha) into neonatal gsd-ia mice failed to sustain their life beyond weaning. we now show that neonatal infusion of gsd-ia mice with an aav ... | 2006 | 16195703 |
| attachment of adeno-associated virus type 3h to fibroblast growth factor receptor 1. | heparan sulfate proteoglycan is thought to act as primary receptor for adeno-associated virus type 2 (aav-2). reported coreceptors include alphavbeta5 integrin, fibroblast growth factor receptor 1 (fgfr-1), and hepatocyte growth factor (c-met). the interaction of aav type 3 (aav-3) with possible cell membrane receptors is incompletely defined. in this study, using assays detecting competition with viral infection, virus binding inhibition assays and dot blotting, we show attachment of aav-3 stra ... | 2006 | 16195782 |
| inhibition of ovarian cancer metastasis by adeno-associated virus-mediated gene transfer of nm23h1 in an orthotopic implantation model. | ovarian cancer is one of the most threatening malignant tumors in females due to the frequent occurrence of metastasis that precedes diagnosis. the present study explored the possibility of preventing ovarian cancer metastasis by promoting nm23h1 expression through adeno-associated virus (aav)-mediated gene transfer. a cell line of high metastatic potential, sw626-m4, was derived by in vivo selection and used to establish an ovarian cancer metastasis model in the mouse. liver metastasis and anim ... | 2006 | 16179930 |
| persistent liver expression of murine apoa-l using vectors based on adeno-associated viral vectors serotypes 5 and 1. | plasma levels of high-density lipoprotein-cholesterol (hdl-c) and apolipoprotein a-l (apoa-l) are inversely related to risk for coronary heart disease. overexpression of apoa-l inhibits atherosclerosis in animal models. a method of stably expressing apoa-l using somatic gene transfer would be of interest. pseudotyped adeno-associated virus (aav) vectors comprised of inverted terminal repeats from aav serotype 2 have been used for liver-directed gene transfers. we hypothesized that liver-directed ... | 2006 | 16099465 |
| noninvasive monitoring of therapeutic gene transfer in animal models of muscular dystrophies. | muscular dystrophies are a genetically and phenotypically heterogeneous group of degenerative muscle diseases. a subset of them are due to genetic deficiencies in proteins which form the dystrophin-associated complex at the membrane of the myofibers. in this report, we utilized recombinant adeno-associated virus containing a u7 cassette carrying an antisense sequence aimed at inducing exon skipping of the dystrophin gene or containing the alpha-sarcoglycan gene to alleviate the dystrophic phenot ... | 2006 | 16107863 |
| isolation, characterization, gene modification, and nuclear reprogramming of porcine mesenchymal stem cells. | bone marrow mesenchymal stem cells (mscs) are adult pluripotent cells that are considered to be an important resource for human cell-based therapies. understanding the clinical potential of mscs may require their use in preclinical large-animal models, such as pigs. the objectives of the present study were 1) to establish porcine msc (pmsc) cultures; 2) to optimize in vitro pmsc culture conditions, 3) to investigate whether pmscs are amenable to genetic manipulation, and 4) to determine pmsc rep ... | 2006 | 16162872 |
| enhanced transduction of mouse bone marrow-derived dendritic cells by repetitive infection with self-complementary adeno-associated virus 6 combined with immunostimulatory ligands. | the potential of adeno-associated virus (aav)-based vectors in human gene therapy is being explored for several diseases. although sustained transgene expression and low vector-associated cellular immunity are attractive features of recombinant (r) aav, the wider application of raav vectors encapsidated in serotype 2 capsid is hampered by poor transduction efficiency in many target tissues. these include ex vivo-generated dendritic cells (dc), which have demonstrated promising immunotherapeutic ... | 2006 | 16136165 |
| apobec3a is a potent inhibitor of adeno-associated virus and retrotransposons. | apobec3 proteins constitute a family of cytidine deaminases that provide intracellular resistance to retrovirus replication and transposition of endogenous retroelements. one family member, apobec3a (ha3a), is an orphan, without any known antiviral activity. we show that ha3a is catalytically active and that it, but none of the other family members, potently inhibits replication of the parvovirus adeno-associated virus (aav). ha3a was also a potent inhibitor of the endogenous ltr retroelements, ... | 2006 | 16527742 |
| a hybrid vector for ligand-directed tumor targeting and molecular imaging. | merging tumor targeting and molecular-genetic imaging into an integrated platform is limited by lack of strategies to enable systemic yet ligand-directed delivery and imaging of specific transgenes. many eukaryotic viruses serve for transgene delivery but require elimination of native tropism for mammalian cells; in contrast, prokaryotic viruses can be adapted to bind to mammalian receptors but are otherwise poor vehicles. here we introduce a system containing cis-elements from adeno-associated ... | 2006 | 16630824 |
| inadvertent germline transmission of aav2 vector: findings in a rabbit model correlate with those in a human clinical trial. | the risk of germline transmission of vector sequences in humans is a major safety concern, because the enrollment of subjects of reproductive age in early-phase clinical trials of gene transfer continues to increase. in a study of adult men with hemophilia b, adeno-associated virus serotype 2 (aav2) delivered to the liver via the hepatic artery resulted in unexpected transient vector dissemination to the semen. here we report that intravenous aav2 injection in rabbits proved a useful model to as ... | 2006 | 16631412 |
| suppression of atherogenesis by delivery of tgfbeta1act using adeno-associated virus type 2 in ldlr knockout mice. | tgfbeta(1) deficiency has been attributed to the development of atherosclerosis. there is, however, little direct evidence for this concept. to examine this hypothesis, low-density lipoprotein receptor knockout (ldlr(-/-)) mice were injected via tail vein with recombinant adeno-associated virus type 2 (raav) carrying a bioactive tgfbeta(1) mutant (aav/tgfbeta1act, n=10) or granulocyte-macrophage-colony stimulating factor (aav/gm-csf, n=10, a negative control) or saline (n=9, control), and then p ... | 2006 | 16631603 |
| a histone deacetylase inhibitor enhances recombinant adeno-associated virus-mediated gene expression in tumor cells. | the transduction of cancer cells using recombinant adeno-associated virus (raav) occurs with low efficiency, which limits its utility in cancer gene therapy. we have previously sought to enhance raav-mediated transduction of cancer cells by applying dna-damaging stresses. in this study, we examined the effects of the histone deacetylase inhibitor fr901228 on tumor transduction mediated by raav types 2 and 5. fr901228 treatment significantly improved the expression of the transgene in four cancer ... | 2006 | 16387551 |
| adeno-associated virus type 2 increases proteosome-dependent degradation of p21waf1 in a human papillomavirus type 31b-positive cervical carcinoma line. | adeno-associated virus type 2 (aav2) seropositivity is negatively correlated with the development of human papillomavirus (hpv)-associated cervical cancer. we have begun analysis of the molecular mechanisms underlying aav2-mediated onco-suppression through cell cycle regulation in hpv-infected keratinocytes isolated from a low-grade cervical lesion. aav2 superinfection of hpv type 31b (hpv31b)-positive cells at early times postinfection resulted in degradation of the cyclin-dependent kinase (cdk ... | 2006 | 16641284 |
| identification and characterization of novel adeno-associated virus isolates in atcc virus stocks. | adeno-associated viruses (aavs) depend on a helper virus for efficient replication. to identify novel aav isolates, we screened a diverse set of virus isolates for the presence of aav dna. aavs found in 10 simian adenovirus isolates showed greater than 96% homology to aav1 and aav6 but had distinct biological properties. two representatives of this group, aav(vr-195) and aav(vr-355), were studied in more detail. while the novel aavs had high sequence homologies and required sialic acid for cell ... | 2006 | 16641301 |
| safety of recombinant adeno-associated virus type 2-rpe65 vector delivered by ocular subretinal injection. | aav2 delivery of the rpe65 gene to the retina of blind rpe65-deficient animals restores vision. this strategy is being considered for human trials in rpe65-associated leber congenital amaurosis (lca), but toxicity and dose efficacy have not been defined. we studied ocular delivery of aav-2/2.rpe65 in rpe65-mutant dogs. there was no systemic toxicity. ocular examinations showed mild or moderate inflammation that resolved over 3 months. retinal histopathology indicated that traumatic lesions from ... | 2006 | 16644289 |
| the "perivascular pump" driven by arterial pulsation is a powerful mechanism for the distribution of therapeutic molecules within the brain. | we investigated the movement of interstitially infused macromolecules within the central nervous system (cns) in rats with high and low blood pressure (bp)/heart rate and in rats euthanized immediately before infusion (no heart action). adeno-associated virus 2 (aav2), fluorescent liposomes, or bovine serum albumin was infused into rat striatum (six hemispheres per group) by convection-enhanced delivery (ced). after infusion, distribution volumes were evaluated. the rats with high bp/heart rate ... | 2006 | 16650807 |
| early, sustained efficacy of adeno-associated virus vector-mediated gene therapy in glycogen storage disease type ia. | the deficiency of glucose-6-phosphatase (g6pase) underlies life-threatening hypoglycemia and growth retardation in glycogen storage disease type ia (gsd-ia). an adeno-associated virus (aav) vector encoding g6pase was pseudotyped as aav8 and administered to 2-week-old gsd-ia mice (n = 9). median survival was prolonged to 7 months following vector administration, in contrast to untreated gsd-ia mice that survived for only 2 weeks. although gsd-ia mice were initially growth-retarded, treated mice i ... | 2006 | 16672983 |
| correlation of human papillomavirus and adeno-associated virus 2 infection in cytology with korean women. | the purpose of our prospective study was to investigate the prevalence of adeno-associated virus (aav) and human papillomavirus (hpv) 16 and/or hpv 18 infection in korean women with normal cervical smears and those with hpv-associated cervical intraepithelial neoplasia (cin) and cancer in cytobrush samples, and to evaluate the correlation between aav 2 and hpv 16 and/or hpv 18 infection. aav 2 was detected in cin i (9.7%), cin ii (20%), cin iii (22.8%), and cancer (10%). hpv 16 was detected in c ... | 2006 | 16681733 |
| utility of intraperitoneal administration as a route of aav serotype 5 vector-mediated neonatal gene transfer. | gene transfer into a fetus or neonate can be a fundamental approach for treating genetic diseases, particularly disorders that have irreversible manifestations in adulthood. although the potential utility of this technique has been suggested, the advantages of neonatal gene transfer have not been widely investigated. here, we tested the usefulness of neonatal gene transfer using adeno-associated virus (aav) vectors by comparing the administration routes and vector doses. | 2006 | 16685745 |
| vascular bed-targeted in vivo gene delivery using tropism-modified adeno-associated viruses. | virus-mediated gene delivery is restricted by the infectivity profile of the chosen vector. targeting the vascular endothelium via systemic delivery has been attempted using peptides isolated in vitro (using either phage or vector display) and implicit reliance on target receptor expression in vivo. this has limited application since endothelial cells in vitro and in vivo differ vastly in receptor profiles and because of the existence of complex endothelial "zip codes" in vivo. we therefore test ... | 2006 | 16387552 |
| separate basic region motifs within the adeno-associated virus capsid proteins are essential for infectivity and assembly. | adeno-associated virus (aav) is gaining momentum as a gene therapy vector for human applications. however, there remain impediments to the development of this virus as a vector. one of these is the incomplete understanding of the biology of the virus, including nuclear targeting of the incoming virion during initial infection, as well as assembly of progeny virions from structural components in the nucleus. toward this end, we have identified four basic regions (br) on the aav2 capsid that repre ... | 2006 | 16699000 |
| elevated rhoa/rho-kinase activity in the aged rat penis: mechanism for age-associated erectile dysfunction. | epidemiologic studies have shown that aging accounts significantly for the prevalence of erectile dysfunction (ed). the pathophysiology of ed during aging and its underlying molecular mechanisms are largely unknown. we hypothesized that increased rhoa/rho-kinase signaling is a major factor in the pathogenesis of age-associated ed and the mechanism involves increased penile smooth muscle contractility through inhibition of myosin light chain phosphatase. male fischer 344 young (4 month old) and a ... | 2006 | 16396994 |
| expression profiles of bovine adeno-associated virus and avian adeno-associated virus display significant similarity to that of adeno-associated virus type 5. | we present the first detailed expression profiles of nonprimate-derived adeno-associated viruses, namely, bovine adeno-associated virus (b-aav) and avian adeno-associated virus (a-aav), which were obtained after the infection of cell lines derived from their natural hosts. in general, the profiles of b-aav and a-aav were quite similar to that of aav5; however, both exhibited features found for aav2 as well. like adeno-associated virus type 5 (aav5), b-aav and a-aav utilized an internal polyadeny ... | 2006 | 16699028 |
| gangliosides are essential for bovine adeno-associated virus entry. | recombinant adeno-associated viruses (aav) are promising gene therapy vectors. we have recently identified a bovine adeno-associated virus (baav) that demonstrates unique tropism and transduction activity compared to primate aavs. to better understand the entry pathway and cell tropism of baav, we have characterized the initial cell surface interactions required for transduction with baav vectors. like a number of aavs, baav requires cell surface sialic acid groups for transduction and virus att ... | 2006 | 16699032 |
| robust systemic transduction with aav9 vectors in mice: efficient global cardiac gene transfer superior to that of aav8. | it has been recently shown that recombinant adeno-associated virus serotype 8 (raav8) is a robust alternative serotype vector that overcomes many of the limitations of raav2 and transduces various tissues efficiently and globally through systemic vector administration. aav9 is a serotype newly isolated from human tissues, but our knowledge of the biology of raav9 in vivo is currently limited. here, we demonstrate by a series of comprehensive side-by-side experiments with raav8 and 9 vectors deli ... | 2006 | 16713360 |
| correction of feline lipoprotein lipase deficiency with adeno-associated virus serotype 1-mediated gene transfer of the lipoprotein lipase s447x beneficial mutation. | human lipoprotein lipase (hlpl) deficiency, for which there currently exists no adequate treatment, leads to excessive plasma triglycerides (tgs), recurrent abdominal pain, and life-threatening pancreatitis. we have shown that a single intramuscular administration of adeno-associated virus (aav) serotype 1 vector, encoding the human lpl(s447x) variant, results in complete, long-term normalization of dyslipidemia in lpl(/) mice. as a prelude to gene therapy for human lpl deficiency, we tested the ... | 2006 | 16716106 |
| chimeric adeno-associated virus/antisense u1 small nuclear rna effectively rescues dystrophin synthesis and muscle function by local treatment of mdx mice. | duchenne muscular dystrophy (dmd) is a x-linked myopathy in which deletions and point mutations in the dystrophin gene abolish dystrophin expression. the defect can often be corrected at the posttranscriptional level by exon skipping. in an animal model of dmd, the mdx mouse, a point mutation in exon 23 of the dystrophin gene introduces a premature stop codon. skipping of this exon reestablishes the open reading frame in the dystrophin mrna. we have obtained persistent exon skipping in mdx mice ... | 2006 | 16716113 |
| gene transfer of trophic factors and stem cell grafting as treatments for parkinson's disease. | current therapies for parkinson's disease (pd) are limited in their ability to control pd symptomatology, are associated with motor and psychiatric side effects, and do not prevent disease progression. considerable scientific and media interest has focused on the potential value of gene and stem cell therapies to overcome these problems and to enhance the quality of life for pd patients. gene therapies utilize a viral vector to deliver a protein of interest to specific brain region. clinical tri ... | 2006 | 16717256 |
| gene therapy of the brain in the dog model of hurler's syndrome. | a defect of the lysosomal enzyme alpha-l-iduronidase (idua) interrupts the degradation of glycosaminoglycans in mucopolysaccharidosis type i, causing severe neurological manifestations in children with hurler's syndrome. delivery of the missing enzyme through stereotactic injection of adeno-associated virus vectors coding for idua prevents neuropathology in affected mice. we examined the efficacy and the safety of this approach in enzyme-deficient dogs. | 2006 | 16718701 |
| efficient aav1-aav2 hybrid vector for gene therapy of hemophilia. | adeno-associated virus (aav) serotype 1 (aav1) has been shown to be more effective than the well-studied aav serotype 2 (aav2) in muscle gene transfer. replacement of amino acids 350 to 430 of aav2 vp1 with the corresponding amino acids from vp1 of aav1 resulted in a hybrid vector, termed aav-221-iv, which behaved similarly to aav1 in vitro and in vivo in muscle. intramuscular injection of 1x10(11) vector particles per mouse of hybrid vector carrying a human fix transgene in cd4 knockout mice re ... | 2006 | 16409124 |
| recombinant adeno-associated viral vector encoding human vegf165 induces neomicrovessel formation in the adult mouse brain. | delivery of therapeutic genes represents a fascinating possibility to accelerate injury-repairing process in tissues that are otherwise difficult to treat, such as cerebral ischemia. current studies indicate that gene transfer-induced focal angiogenesis in the brain may provide an important therapeutic strategy. in the present study, we reported the efficacy of induction of angiogenesis with an adeno-associated virus (aav) vector expressing the 165 amino acid isoform of vascular endothelial grow ... | 2006 | 16720385 |
| adeno-associated virus-2 (aav-2) causes trophoblast dysfunction, and placental aav-2 infection is associated with preeclampsia. | shallow invasion by extravillous trophoblast cells into the uterine wall reduces placental perfusion and causes placental dysfunction, but the one or more causes of shallow placental invasion are unknown. we hypothesized that infection with adeno-associated virus-2 (aav-2) inhibits trophoblast invasion and is associated with preeclampsia, which is a common obstetric complication resulting from placental dysfunction. we determined that transformed extravillous trophoblast (htr-8/svneo) cells were ... | 2006 | 16723710 |
| systemic correction of a fatty acid oxidation defect by intramuscular injection of a recombinant adeno-associated virus vector. | mitochondrial beta-oxidation of fatty acids is required to meet physiologic energy requirements during illness and periods of fasting or physiologic stress, and is most active in liver and striated muscle. acyl-coa dehydrogenases of varying chain-length specificities represent the first step in the mitochondria for each round of beta-oxidation, each of which removes two-carbon units as acetyl-coa for entry into the tricarboxylic acid cycle. we have used recombinant adeno-associated virus (raav) ... | 2006 | 16409126 |
| astrocytic expression of transgene in the rat brain mediated by baculovirus vectors containing an astrocyte-specific promoter. | 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 (c ... | 2006 | 16724097 |
| recombinant adeno-associated viral vectors as therapeutic agents to treat neurological disorders. | recombinant adeno-associated virus (raav) is derived from a small human parvovirus with an excellent safety profile. in addition, this viral vector efficiently transduces and supports long-term transgene expression in the nervous system. these properties make raav a reasonable candidate vector for treating neurological disorders. indeed, raav is currently being used in five early stage clinical trials for various neurodegenerative disorders. therefore, we will review the currently available prec ... | 2006 | 16412695 |
| inhibition of human nasopharyngeal carcinoma growth and metastasis in mice by adenovirus-associated virus-mediated expression of human endostatin. | nasopharyngeal carcinoma (npc) is a highly malignant and frequently metastasized tumor. endostatin has been shown to inhibit npc growth, but its efficacy against npc metastasis has not been shown in vivo. here, we established a npc metastasis model in mice by transplanting ebv-positive npc cells, c666-1, in the livers of nude mice and observed lung metastasis. furthermore, we showed that tail vein injection of recombinant adeno-associated virus encoding human endostatin (raav-hendo) significantl ... | 2006 | 16731762 |
| characterization of the capsid protein glycosylation of adeno-associated virus type 2 by high-resolution mass spectrometry. | adeno-associated virus type 2 (aav-2) capsid proteins have eight sequence motifs that are potential sites for o- or n-linked glycosylation. three are in prominent surface locations, close to the sites of cellular receptor attachment and to neutralizing epitopes on or near protrusions surrounding the three-fold axes, raising the possibility that aav-2 might use glycosylation as a means of immune escape or for preventing reattachment on release of progeny virus. peptide mapping and structural anal ... | 2006 | 16731956 |
| high-level transgene expression in nonhuman primate liver with novel adeno-associated virus serotypes containing self-complementary genomes. | adeno-associated virus (aav) vectors are being considered for in vivo applications of gene therapy in the treatment of a variety of disorders. this study evaluates the biology of second-generation vectors based on the novel serotypes aav7 and aav8 and containing self-complementary genomes in the nonhuman primate liver. stable levels of transgene expression were achieved in cynomolgus macaques and suggest efficiencies at least 2 log higher than what could be achieved with aav2 vectors using tradi ... | 2006 | 16731960 |
| actin binding activity of subunit b of vacuolar h+-atpase is involved in its targeting to ruffled membranes of osteoclasts. | adeno-associated virus was used to transduce primary mouse osteoclasts with the b1 isoform of vacuolar h(+)-atpase. b1, which is not normally expressed in osteoclasts, was correctly targeted to ruffled membranes of resorbing osteoclasts. mutant subunit b1 that lacked a functional actin-binding site did not accumulate in ruffled membranes. | 2006 | 16734386 |
| detection of adeno-associated virus type 2 genome in cervical carcinoma. | adeno-associated virus (aav) can impair the replication of other viruses. adeno-associated virus seroprevalences have been reported to be lower among women with cervical cancer. in-vitro, aav can interfere with the production of human papillomavirus virions. adeno-associated virus-2 dna has also been detected in cervical cancer tissue, although not consistently. to evaluate the role of aav infection in relation to invasive cervical cancer, we performed a nested case-control study within a retros ... | 2006 | 16736006 |
| recombinant baculovirus containing the diphtheria toxin a gene for malignant glioma therapy. | insect baculoviruses are capable of infecting mammalian glial cells in the central nervous system. we investigated in the current study the feasibility of using the viruses as toxin gene vectors to eliminate malignant glioma cells in the brain. we first confirmed that glioma cells were permissive to baculovirus infection, with variable transduction efficiencies at 100 viral particles per cell and ranging between 35% and 70% in seven human and rat glioma cell lines. we then developed a recombinan ... | 2006 | 16740719 |