Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
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| identification of adeno-associated virus contamination in cell and virus stocks by pcr. | to further understand the biology of adeno-associated virus (aav) and identify the presence of aav in laboratory samples, we have developed a sensitive pcr-based assay using degenerate primers based on the sequence of seven diverse aav isolates. using these primers, we can detect free virus in viral stocks, cleared cell lysate, as well as in latently infected cells. the method can detect as little as 10 viral copies/microl of sample and can be adapted for high-throughput screening technology. wi ... | 2004 | 15088385 |
| gene therapy platform for bone regeneration using an exogenously regulated, aav-2-based gene expression system. | viral delivery of the therapeutic gene bone morphogenetic protein-2 (bmp-2) is a promising approach for bone regeneration. the human parvovirus adeno-associated virus (aav) type 2 is considered one of the most encouraging viral vector systems because of its high transduction rates and biosafety ratings. bone morphogenetic protein-2 is a highly potent osteoinductive protein, which induces bone formation in vivo and osteogenic differentiation in vitro. the exogenous regulation of bmp-2 expression ... | 2004 | 15093189 |
| induction of antigen-specific cd4+ t-cell anergy and deletion by in vivo viral gene transfer. | immune responses to the therapeutic gene product are a potentially serious complication in treatment of genetic disease by gene therapy. induction and maintenance of immunologic hypo-responsiveness to the therapeutic antigen is therefore critical to the success of gene-based treatment of inherited protein deficiency. here, we demonstrate induction of antigen-specific cd4+ t-cell tolerance to a secreted transgene product (ovalbumin, ova) in ova-specific t-cell receptor (tcr) transgenic mice by he ... | 2004 | 15105293 |
| efficient prnp gene targeting in bovine fibroblasts by adeno-associated virus vectors. | gene-targeted livestock can be created by combining ex vivo manipulation of cultured nuclear donor cells with cloning by nuclear transfer. however, this process can be limited by the low gene targeting frequencies obtained by transfection methods, and the limited ex vivo life span of the normal nuclear donor cells. we have developed an alternative gene targeting method based on the delivery of linear, single-stranded dna molecules by adeno-associated virus (aav) vectors, which can be used to int ... | 2004 | 15107244 |
| recombinant adeno-associated virus type 2-mediated gene delivery into the rpe65-/- knockout mouse eye results in limited rescue. | background: leber's congenital amaurosis (lca) is a severe form of retinal dystrophy. mutations in the rpe65 gene, which is abundantly expressed in retinal pigment epithelial (rpe) cells, account for approximately 10-15% of lca cases. in this study we used the high turnover, and rapid breeding and maturation time of the rpe65-/- knockout mice to assess the efficacy of using raav-mediated gene therapy to replace the disrupted rpe65 gene. the potential for raav-mediated gene treatment of lca was t ... | 2004 | 15109394 |
| construction of adeno-associated virus coexpression system for human angiopoietin-1 and vegf gene. | ischemic disease is one of the leading causes of death in the world. in order to further study gene therapy for ischemic disease, we constructed a recombinant plasmid for co-expression of human angiopoietin-1 and vascular endothelial growth factor 165(vegf165) gene in adeno-associated virus (aav) gene delivery system. | 2004 | 15109450 |
| gene therapy for als delivers. | amyotrophic lateral sclerosis (als) is a fatal, progressive neurodegenerative disease that kills motor neurons. despite a long disappointing history of human trials with neurotrophins, including insulin-like growth factor 1 (igf-1), kaspar and colleagues have successfully slowed disease in transgenic als mice by forcing motor neurons to produce igf-1 following retrograde delivery of recombinant adeno-associated virus (aav) injected into muscle. with the clinical safety of both igf-1 and aav alre ... | 2004 | 15111001 |
| mia (melanoma inhibitory activity) promoter mediated tissue-specific suicide gene therapy of malignant melanoma. | suicide gene therapy of malignant melanoma essentially requires efficient gene transfer and highly selective therapeutic gene expression. to achieve this, recombinant adeno-associated virus (raav) particles were constructed containing the tissue-specific promoter of the human melanoma inhibitory activity (hmia) gene combined with four copies of the enhancer element of the murine tyrosinase gene. three melanoma and one cervix carcinoma cell line were infected with raav particles carrying a report ... | 2004 | 15118759 |
| preclinical gene therapy studies for hemophilia using adeno-associated virus (aav) vectors. | gene therapy offers a potential cure for hemophilia and several gene transfer vectors have been evaluated for their ability to treat this disease. this article reviews the studies that have been performed to evaluate the ability of recombinant adeno-associated virus (aav) vectors to achieve safely the sustained expression of clotting factors following intramuscular, intravenous, and intrahepatic delivery to several animal models. these routes of administration are all effective in providing sust ... | 2004 | 15118928 |
| separate control of rep and cap expression using mutant and wild-type loxp sequences and improved packaging system for adeno-associated virus vector production. | adeno-associated virus (aav) vectors are a practical choice for gene transfer, and demand for them is increasing. to cope with the necessity in the near future, we have developed a number of approaches to establish packaging cell lines for the production of aav vectors. in our previous study, a highly regulated expression of large rep proteins was obtained by using the cre-loxp switching system. therefore, in the present study, to regulate cap expression as well, we developed an inducible expres ... | 2004 | 15122043 |
| successful gene transfer using adeno-associated virus vectors into the kidney: comparison among adeno-associated virus serotype 1-5 vectors in vitro and in vivo. | gene transfer into the kidney has great potential as a novel therapeutic approach. however, an efficient method of gene transfer into the kidney has not been established. we explored the transduction efficiency of renal cells in vitro and in vivo using adeno-associated virus (aav) serotype 1-5 vectors encoding the beta-galactosidase gene. | 2004 | 15122061 |
| gene transfer into rabbit arteries with adeno-associated virus and adenovirus vectors. | gene transfer offers considerable potential for altering vessel wall physiology and intervention in vascular disease. therefore, there is great interest in developing optimal strategies and vectors for efficient, targeted gene delivery into a vessel wall. | 2004 | 15133765 |
| identification of a replication-defective herpes simplex virus for recombinant adeno-associated virus type 2 (raav2) particle assembly using stable producer cell lines. | the development of stable producer cell lines for recombinant adeno-associated virus (raav) assembly is a strategy followed by many groups to develop scalable production methods suitable for good manufacturing practice (gmp) requirements. the major drawback of this method lies in the requirement for replicating adenovirus (ad) for raav assembly. in the present study, we analyzed the ability of several replication-defective herpes simplex type 1 (hsv-1) helper viruses to induce raav2 particle pro ... | 2004 | 15133766 |
| basic fibroblast growth factor enhances transduction, distribution, and axonal transport of adeno-associated virus type 2 vector in rat brain. | the ubiquitous expression of cell surface heparan sulfate proteoglycan, a binding receptor for adeno-associated virus type 2 (aav-2), may account for the broad host range of this vector. because the fibroblast growth factor receptor type 1 has been postulated to be a coreceptor for successful aav-2 entry into host cells, we designed a strategy to investigate whether coadministration of this virus with basic fibroblast growth factor (bfgf) can enhance aav-2-mediated gene delivery. we injected aav ... | 2004 | 15144577 |
| circulating anti-wild-type adeno-associated virus type 2 (aav2) antibodies inhibit recombinant aav2 (raav2)-mediated, but not raav5-mediated, gene transfer in the brain. | epidemiological studies report that 80% of the population maintains antibodies (ab) to wild-type (wt) adeno-associated virus type 2 (aav2), with 30% expressing neutralizing ab (nab). the blood-brain barrier (bbb) provides limited immune privilege to brain parenchyma, and the immune response to recombinant aav (raav) administration in the brain of a naive animal is minimal. however, central nervous system transduction in preimmunized animals remains unstudied. vector administration may disrupt th ... | 2004 | 15163728 |
| clades of adeno-associated viruses are widely disseminated in human tissues. | the potential for using adeno-associated virus (aav) as a vector for human gene therapy has stimulated interest in the dependovirus genus. serologic data suggest that aav infections are prevalent in humans, although analyses of viruses and viral sequences from clinical samples are extremely limited. molecular techniques were used in this study to successfully detect endogenous aav sequences in 18% of all human tissues screened, with the liver and bone marrow being the most predominant sites. seq ... | 2004 | 15163731 |
| cloning and characterization of a bovine adeno-associated virus. | to better understand the relationship between primate adeno-associated viruses (aavs) and those of other mammals, we have cloned and sequenced the genome of an aav found as a contaminant in two isolates of bovine adenovirus that was reported to be serologically distinct from primate aavs. the bovine aav (baav) genome has 4,693 bp, and its organization is similar to that of other aav isolates. the left-hand open reading frame (orf) and both inverted terminal repeats (itrs) have the highest homolo ... | 2004 | 15163744 |
| adeno-associated virus type 2 vp2 capsid protein is nonessential and can tolerate large peptide insertions at its n terminus. | direct insertion of amino acid sequences into the adeno-associated virus type 2 (aav) capsid open reading frame (cap orf) is one strategy currently being developed for retargeting this prototypical gene therapy vector. while this approach has successfully resulted in the formation of aav particles that have expanded or retargeted viral tropism, the inserted sequences have been relatively short, linear receptor binding ligands. since many receptor-ligand interactions involve nonlinear, conformati ... | 2004 | 15163751 |
| improved transduction of primary murine hepatocytes by recombinant adeno-associated virus 2 vectors in vivo. | adeno-associated virus 2 (aav) vectors are currently in use in phase i/ii clinical trials for gene therapy of cystic fibrosis and hemophilia b. although 100% of murine hepatocytes can be targeted by aav vectors, the transgene expression is limited to approximately 5% of hepatocytes. since the viral genome is a single-stranded dna, and single strands of both polarities are encapsidated with equal frequency, it has been suggested that failure to undergo dna strand-annealing accounts for the lack o ... | 2004 | 15164097 |
| rescue of enzyme deficiency in embryonic diaphragm in a mouse model of metabolic myopathy: pompe disease. | several human genetic diseases that affect striated muscle have been modeled by creating knockout mouse strains. however, many of these are perinatal lethal mutations that result in death from respiratory distress within hours after birth. as the diaphragm muscle does not contract until birth, the sudden increase in diaphragm activity creates permanent injury to the muscle causing it to fail to meet respiratory demands. therefore, the impact of these mutations remains hidden throughout embryonic ... | 2004 | 15169761 |
| gene therapy with novel adeno-associated virus vectors substantially diminishes atherosclerosis in a murine model of familial hypercholesterolemia. | familial hypercholesterolemia is an inherited disease caused by mutations in the ldl receptor gene leading to severe hypercholesterolemia and atherosclerosis. the ldl receptor is predominantly expressed in the liver, making it a preferred target organ for somatic gene therapy. we recently isolated a new family of vectors based on adeno-associated viruses (aavs) isolated from nonhuman primates, which enable efficient and stable transgene expression following in vivo gene delivery to liver. | 2004 | 15170737 |
| recombinant adeno-associated virus-mediated kallikrein gene therapy reduces hypertension and attenuates its cardiovascular injuries. | gene therapy of hypertension requires long-term expression of a therapeutic gene to achieve stable reduction of blood pressure. human tissue kallikrein (hk) cleaves kininogen to produce a potent vasoactive peptide kinin, which plays an important role in the regulation of the cardiovascular and renal functions. in the present study, we have delivered human kallikrein cdna with an raav vector to explore the potential therapeutic effects of kallikrein on hypertension and related secondary complicat ... | 2004 | 15175642 |
| novel approaches to augment adeno-associated virus type-2 endocytosis and transduction. | recombinant adeno-associated virus (raav) receptor binding, endocytosis, nuclear trafficking and second strand gene conversion have been described as potential rate-limiting steps in raav type-2 (raav-2) transduction. several strategies have been developed to enhance raav-2 intracellular trafficking and gene conversion in an attempt to increase the efficiency of this virus as a gene therapy vector. to this end, the current study has investigated novel methods for augmenting raav transduction by ... | 2004 | 15177892 |
| creation of a mouse expressing defective human factor ix. | the majority of cases of human hemophilia b are the result of missense mutations in the coagulation factor ix gene and defective circulating factor ix is detectable in most patients. the available mouse factor ix knockout models of hemophilia b (fixko mouse) reproduce the bleeding phenotype of human hemophilia b, but because the models produce no factor ix they fail to reproduce the dominant human phenotype. we have created a human factor ix mouse model of hemophilia b (r333q-hfix mouse) by homo ... | 2004 | 15178576 |
| long-term enzymatic and phenotypic correction in the phenylketonuria mouse model by adeno-associated virus vector-mediated gene transfer. | phenylketonuria (pku) is an autosomal recessive metabolic disorder caused by a deficiency of phenylalanine hydroxylase (pah). the accumulation of phenylalanine leads to severe mental and psychomotor retardation, and hypopigmentation of skin and hair. low-phenylalanine diet therapy can prevent irreversible damage if instituted from birth. however, poor compliance with the strict lifelong dietary therapy leads to various neurologic and behavioral problems. to develop a safe and promising gene ther ... | 2004 | 15181195 |
| in vivo gene delivery to articular chondrocytes mediated by an adeno-associated virus vector. | (1) to investigate the efficiency of direct in vivo adeno-associated virus (aav) vector-mediated gene transduction to chondrocytes in relation to normal and injured articular cartilage. (2) to evaluate the effects of ultra-violet light-activated gene transduction (lagt) in chondrocytes in vivo. (3) to determine dissemination of active raav vector after intra-articular administration. | 2004 | 15183427 |
| rhoa/rho-kinase suppresses endothelial nitric oxide synthase in the penis: a mechanism for diabetes-associated erectile dysfunction. | significant impairment in endothelial-derived nitric oxide is present in the diabetic corpus cavernosum. rhoa/rho-kinase may suppress endothelial nitric oxide synthase (enos). here, we tested the hypothesis that rhoa/rho-kinase contributes to diabetes-related erectile dysfunction and down-regulation of enos in the streptozotocin (stz)-diabetic rat penis. colocalization of rho-kinase and enos protein was present in the endothelium of the corpus cavernosum. rhoa/rho-kinase protein abundance and my ... | 2004 | 15184671 |
| the recombinant adeno-associated virus vector (raav2)-mediated apolipoprotein b mrna-specific hammerhead ribozyme: a self-complementary aav2 vector improves the gene expression. | background: in humans, overproduction of apolipoprotein b (apob) is positively associated with premature coronary artery diseases. to reduce the levels of apob mrna, we have designed an apob mrna-specific hammerhead ribozyme targeted at nucleotide sequences gua6679 (rb15) mediated by adenovirus, which efficiently cleaves and decreases apob mrna by 80% in mouse liver and attenuates the hyperlipidemic condition. in the current study, we used an adeno-associated virus vector, serotype 2 (aav2) and ... | 2004 | 15193153 |
| [construction and expression of adeno-associated virus vectors of smad 6 and smad 7 genes in human renal tubule epithelial cells]. | to construct the adeno-associated virus(aav) vectors of smad 6 and smad 7 genes and observe their expressions in human renal tubule epithelial cells. | 2004 | 15193216 |
| adeno-associated virus 2-mediated gene therapy decreases autofluorescent storage material and increases brain mass in a murine model of infantile neuronal ceroid lipofuscinosis. | infantile neuronal ceroid lipofuscinosis (incl) is the earliest onset form of a class of inherited neurodegenerative disease called batten disease. incl is caused by a deficiency in the lysosomal enzyme palmitoyl protein thioesterase-1 (ppt1). autofluorescent storage material accumulates in virtually all tissues in incl patients, including the brain, and leads to widespread neuronal loss and cortical atrophy. to determine the efficacy of viral-mediated gene therapy, we injected a recombinant ade ... | 2004 | 15193292 |
| inverted terminal repeat sequences of adeno-associated virus enhance the antibody and cd8(+) responses to a hiv-1 p55gag/lamp dna vaccine chimera. | the immune responses to an hiv-1 p55gag vaccine encoded as a dna chimera with the lysosomal associated membrane protein-1 (lamp) have been examined for the effect of the addition of the inverted terminal repeat (itr) sequences of the adeno-associated virus (aav) to the dna plasmid construct, and of packaging the lamp/gag gene as a recombinant aav vector (raav). dna plasmids encoding gag and the lamp/gag protein chimera were constructed in two vectors, the pcdna3.1 and a corresponding plasmid con ... | 2004 | 15193918 |
| correction of metabolic, craniofacial, and neurologic abnormalities in mps i mice treated at birth with adeno-associated virus vector transducing the human alpha-l-iduronidase gene. | murine models of lysosomal storage diseases provide an opportunity to evaluate the potential for gene therapy to prevent systemic manifestations of the disease. to determine the potential for treatment of mucopolysaccharidosis type i using a gene delivery approach, a recombinant adeno-associated virus (aav) vector, vtrca1, transducing the human iduronidase (idua) gene was constructed and 1 x 10(10) particles were injected intravenously into 1-day-old idua(-/-) mice. high levels of idua activity ... | 2004 | 15194053 |
| potent inhibition of arterial intimal hyperplasia by timp1 gene transfer using aav vectors. | seminal to the process of arterial restenosis after balloon angioplasty is extracellular matrix degradation by metalloproteinases (mmps); activity of these proteins is strongly inhibited by the tissue inhibitors of mmps (timps). here we exploit gene transfer using an adeno-associated virus (aav) for timp1 gene delivery in a rat model of intimal hyperplasia. high-titer aav-timp1 efficiently transduced human coronary artery smooth muscle cells (smcs) in vitro and inhibited the capacity of these ce ... | 2004 | 15194054 |
| transduction profiles of recombinant adeno-associated virus vectors derived from serotypes 2 and 5 in the nigrostriatal system of rats. | we compared the transduction efficiencies and tropisms of titer-matched recombinant adeno-associated viruses (raav) derived from serotypes 2 and 5 (raav-2 and raav-5, respectively) within the rat nigrostriatal system. the two serotypes (expressing enhanced green fluorescent protein [egfp]) were delivered by stereotaxic surgery into the same animals but different hemispheres of the striatum (str), the substantia nigra (sn), or the medial forebrain bundle (mfb). while both serotypes transduced neu ... | 2004 | 15194756 |
| gene transfer of nitric oxide synthase via the use of adeno-associated virus vectors. | adeno-associated virus (aav) is a replication-defective dependovirus and is not known to cause disease in humans. aav vectors have a broad host range and can transduce both dividing and nondividing cells. five primate aav serotypes have been characterized in the literature and are designated as aav types 1-5 (aav1-5). there is divergence in homology and tropism for various aav serotypes. aav vectors can be produced by triple plasmids transfection system (adenovirus-free system) and purified by u ... | 2004 | 15199248 |
| models of dilated cardiomyopathy in small animals and novel positive inotropic therapies. | several randomized clinical trials of vesnarinone and milrinone in patients with heart failure left disappointing results in the 1990s. thereafter, use of positive inotropic agents has been avoided. exceptions are the use of digitalis glycosides to treat mild-moderate heart failure and the intravenous administration of catecholamines and phosphodiesterase inhibitors in patients with acute and/or refractory heart failure. it is not, however, exactly known whether chronic enhancement of cardiac co ... | 2004 | 15201171 |
| therapeutic gene transfer for rheumatoid arthritis. | rheumatoid arthritis (ra) is a severe autoimmune systemic disease. chronic synovial inflammation results in destruction of the joints. no conventional treatment is efficient in ra. gene therapy of ra targets mainly the players of inflammation or articular destruction: tnf-alpha or il-1 blocking agents (such as anti-tnf-alpha monoclonal antibodies, soluble tnf-alpha receptor, type ii soluble receptor of il-1, il-1 receptor antagonist), anti-inflammatory cytokines (such as il-4, il-10, il-1), grow ... | 2004 | 15201941 |
| tracing axons of peripheral nerves in rats: a potential technique to study the equine recurrent laryngeal nerve. | to study the fascicular anatomy of peripheral nerves, three different groups of retrograde axonal tracers were evaluated: fluorophores, horseradish peroxidase conjugated to subunit b of cholera toxin (ct-hrp), and adeno-associated virus (aav). the hindlimb nerves in rats served as a model to identify the most efficient tracer in regard to labeling axons within peripheral nerves. the rat's tibial and common peroneal nerves were injected with the different tracers and the sciatic nerve was subsequ ... | 2004 | 15204959 |
| adeno-associated virus vectors integrate at chromosome breakage sites. | adeno-associated virus (aav) vectors transduce cells by multiple pathways, including integration at nonhomologous chromosomal locations by an unknown mechanism. we reasoned that spontaneous chromosome breaks may facilitate vector integration and investigated this in cells containing a specific chromosomal double-strand break created by the endonuclease i-scei or multiple breaks created by treatment with etoposide or gamma-irradiation. vector proviruses were found at i-scei cleavage sites, and se ... | 2004 | 15208627 |
| analysis of the interaction between adeno-associated virus and heparan sulfate using atomic force microscopy. | adeno-associated virus (aav) has been widely used as a viral vector to deliver genes to animal and human tissues in gene therapy studies. both aav-2 and aav-3 use cell surface heparan sulfate (hs), a highly sulfated polysaccharide, as a receptor to establish infections. in this study, we used atomic force microscopy (afm) to investigate the interaction of hs and aav. a silicon chip functionalized with hs was used as a substrate for binding aav for afm analysis. to validate our approach, we found ... | 2004 | 15215232 |
| longterm recombinant adeno-associated, virus-mediated, liver-generated expression of an angiogenesis inhibitor improves survival in mice with disseminated neuroblastoma. | 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. the purpose of this study was to attempt to restrict the growth of disseminated neuroblastoma through delivery of a truncated, soluble form of the vascular endothelial growth factor receptor-2 (vegfr-2 fetal liver kinase [flk]-1), a decoy receptor for vegf. | 2004 | 15217634 |
| restoration of receptor-type protein tyrosine phosphatase eta function inhibits human pancreatic carcinoma cell growth in vitro and in vivo. | dep-1/hptpeta, a receptor-type protein tyrosine phosphatase, is a candidate tumor suppressor gene because its expression was blocked in rat and human thyroid transformed cells, and its restoration reverted their neoplastic phenotype. in addition, loss of dep-1/hptpeta heterozygosity has been described in mammary, lung and colon primary tumors. we now show that dep-1/hptpeta is drastically reduced in several cell lines originating from human epithelial pancreatic carcinomas compared with normal p ... | 2004 | 15231692 |
| inhibition of nf-kappab mediated inflammation by sirna expressed by recombinant adeno-associated virus. | nf-kappab mediated inflammation is a key process to many diseases. rna interference (rnai) is the specific suppression of genes by short double-stranded rna. it was the aim of the present study to modify nf-kappabdependent inflammation by small interfering rna (sirna) expressed by recombinant adeno-associated virus (raav). to study the kinetics of raav mediated expression of sirna, the expression of the luciferase gene was targeted and resulted in a significant decrease of luciferase activity as ... | 2004 | 15234817 |
| rnai suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. | the dominant polyglutamine expansion diseases, which include spinocerebellar ataxia type 1 (sca1) and huntington disease, are progressive, untreatable, neurodegenerative disorders. in inducible mouse models of sca1 and huntington disease, repression of mutant allele expression improves disease phenotypes. thus, therapies designed to inhibit expression of the mutant gene would be beneficial. here we evaluate the ability of rna interference (rnai) to inhibit polyglutamine-induced neurodegeneration ... | 2004 | 15235598 |
| cloning of a novel apaf-1-interacting protein: a potent suppressor of apoptosis and ischemic neuronal cell death. | cytochrome c-initiated activation of apoptotic protease activating factor-1 (apaf-1) is a key step in the mitochondrial-signaling pathway for the activation of death-executing caspases in apoptosis. this signaling pathway has been implicated in the pathophysiology of various neurological disorders, including ischemic brain injury. in this study, we have cloned a novel rat gene product, designated as apaf-1-interacting protein (aip), which functions as a dominant-negative inhibitor of the apaf-1- ... | 2004 | 15240811 |
| immune responses to recombinant adeno-associated virus vectors: putting preclinical findings into perspective. | 2004 | 15242531 | |
| antitumor effect of a novel adeno-associated virus vector targeting to telomerase activity in tumor cells. | telomerase activity is a wide tumor marker. human telomerase reverse transcriptase (htert), the catalytic subunit of the telomerase, is transcriptionally upregulated exclusively in about 90% of cancer cells. in this study, we constructed a novel adeno-associated virus (aav) vector containing the human interferon-beta (hifn-beta) gene under the control of htert promoter (aav-htert-hifn-beta) and investigated its antitumor effect against various human cancer cells in vitro. aav-htert-hifn-beta dis ... | 2004 | 15248024 |
| adeno-associated virus site-specific integration and aavs1 disruption. | adeno-associated virus (aav) is a single-stranded dna virus with a unique biphasic lifestyle consisting of both a productive and a latent phase. typically, the productive phase requires coinfection with a helper virus, for instance adenovirus, while the latent phase dominates in healthy cells. in the latent state, aav is found integrated site specifically into the host genome at chromosome 19q13.4 qtr (aavs1), the only animal virus known to integrate in a defined location. in this study we inves ... | 2004 | 15254160 |
| the microphthalmia transcription factor (mitf) controls expression of the ocular albinism type 1 gene: link between melanin synthesis and melanosome biogenesis. | melanogenesis is the process that regulates skin and eye pigmentation. albinism, a genetic disease causing pigmentation defects and visual disorders, is caused by mutations in genes controlling either melanin synthesis or melanosome biogenesis. here we show that a common transcriptional control regulates both of these processes. we performed an analysis of the regulatory region of oa1, the murine homolog of the gene that is mutated in the x-linked form of ocular albinism, as oa1's function affec ... | 2004 | 15254223 |
| recombinant adeno-associated virus vectors for gene therapy. | recombinant adeno-associated virus (raav) vectors are based on a non-pathogenic human parvovirus (aav) that is unique in its ability to persist in human cells without causing any pathologic effects. studies of the potential barriers to raav-mediated transduction of relatively resistant cells has led to an understanding of the mechanisms of cell attachment and entry, cytoplasmic translocation, nuclear entry, conversion to active double-stranded dna, activation of transcription and establishment o ... | 2004 | 15268676 |
| the adenovirus e1a and e1b19k genes provide a helper function for transfection-based adeno-associated virus vector production. | although the adenoviral e1, e2a, e4 and va rna regions are required for efficient adeno-associated virus (aav) vector production, the role that the individual e1 genes (e1a, e1b19k, e1b55k and protein ix) play in aav vector production has not been clearly determined. e1 mutants were analysed for their ability to mediate aav vector production in hela or kb cells, when cotransfected with plasmids encoding all other packaging functions. disruption of e1a and e1b19k genes resulted in vector yield re ... | 2004 | 15269360 |
| engagement of the b-cell antigen receptor (bcr) allows efficient transduction of zap-70-positive primary b-cll cells by recombinant adeno-associated virus (raav) vectors. | engagement of the b-cell antigen receptor (bcr) by crosslinking of the surface immunoglobulin (sig) homodimer was studied for recombinant adeno-associated virus (raav)-mediated gene transfer into b-cell chronic lymphocytic leukaemia (b-cll) cells. leukemic cells obtained from 20 patients were stimulated with anti-sig-directed antibodies and transduced with raav vectors coding for enhanced green fluorescent protein (egfp) (aav/egfp) or cd40l (aav/cd40l). transduction of b-cll cells was enhanced a ... | 2004 | 15269708 |
| pdgf-d induces macrophage recruitment, increased interstitial pressure, and blood vessel maturation during angiogenesis. | platelet-derived growth factor-d (pdgf-d) is a recently characterized member of the pdgf family with unknown in vivo functions. we investigated the effects of pdgf-d in transgenic mice by expressing it in basal epidermal cells and then analyzed skin histology, interstitial fluid pressure, and wound healing. when compared with control mice, pdgf-d transgenic mice displayed increased numbers of macrophages and elevated interstitial fluid pressure in the dermis. wound healing in the transgenic mice ... | 2004 | 15271796 |
| systemic delivery of genes to striated muscles using adeno-associated viral vectors. | a major obstacle limiting gene therapy for diseases of the heart and skeletal muscles is an inability to deliver genes systemically to muscles of an adult organism. systemic gene transfer to striated muscles is hampered by the vascular endothelium, which represents a barrier to distribution of vectors via the circulation. here we show the first evidence of widespread transduction of both cardiac and skeletal muscles in an adult mammal, after a single intravenous administration of recombinant ade ... | 2004 | 15273747 |
| characterization of the mouse adeno-associated virus aavs1 ortholog. | the nonpathogenic human adeno-associated virus (aav) has developed a mechanism to integrate its genome into human chromosome 19 at 19q13.4 (termed aavs1), thereby establishing latency. here, we provide evidence that the chromosomal signals required for site-specific integration are conserved in the mouse genome proximal to the recently identified mbs85 gene. these sequence motifs can be specifically nicked by the viral rep protein required for the initiation of site-specific aav dna integration. ... | 2004 | 15280500 |
| suicide gene therapy of sarcoma cell lines using recombinant adeno-associated virus 2 vectors. | soft-tissue sarcomas are mesenchymal tumors that respond poorly to systemic chemotherapy. suicide gene therapy may be an alternative treatment strategy. here we show a high susceptibility of human sarcoma cell lines for recombinant adeno-associated virus 2 (raav-2) suicide vectors: connective tissue sarcoma (hs-1), fibrosarcoma (ht-1080), ewing sarcoma (rd-es), askin tumor (sk-n-mc), rhabdomyosarcoma (a-204) and soft-tissue sarcoma (wskl-1). several vectors containing the thymidine kinase (tk) g ... | 2004 | 15280909 |
| the structure of human parvovirus b19. | human parvovirus b19 is the only parvovirus known to be a human pathogen. the structure of recombinant b19-like particles has been determined to approximately 3.5-a resolution by x-ray crystallography and, to our knowledge, represents the first near-atomic structure of an erythrovirus. the polypeptide fold of the major capsid protein vp2 is a "jelly roll" with a beta-barrel motif similar to that found in many icosahedral viruses. the large loops connecting the strands of the beta-barrel form sur ... | 2004 | 15289612 |
| topoisomerase inhibitors enhance the cytocidal effect of aav-hsvtk/ganciclovir on head and neck cancer cells. | adeno-associated virus (aav) is a non-pathogenic virus with a single-strand dna genome. aav vectors have several unique properties suited for gene therapy applications. however, an obstacle to their application is a low efficiency of transgene expression, mainly due to a limited second-strand synthesis. previously, we reported that gamma-rays enhanced the transduction efficiency and cytocidal effect of aav vector harboring the herpes simplex virus-thymidine kinase (aavtk) and ganciclovir (gcv) s ... | 2004 | 15289876 |
| the potential of gene transfer into primary b-cll cells using recombinant virus vectors. | despite recent advances, chronic lymphocytic leukemia (cll) as the most common leukemia remains a largely incurable disease. modern treatment options include novel drugs like purine analogues, monoclonal antibodies and transplantation strategies. moreover, gene transfer of immunostimulatory molecules is another, but still experimental approach that can be used to potentiate immune responses against leukemic cells. cd40 ligand (cd40l) was shown to be a promising molecule for immunotherapy of b-cl ... | 2004 | 15291346 |
| homer proteins regulate sensitivity to cocaine. | drug addiction involves complex interactions between pharmacology and learning in genetically susceptible individuals. members of the homer gene family are regulated by acute and chronic cocaine administration. here, we report that deletion of homer1 or homer2 in mice caused the same increase in sensitivity to cocaine-induced locomotion, conditioned reward, and augmented extracellular glutamate in nucleus accumbens as that elicited by withdrawal from repeated cocaine administration. moreover, ad ... | 2004 | 15294147 |
| recombinant aav viral vectors pseudotyped with viral capsids from serotypes 1, 2, and 5 display differential efficiency and cell tropism after delivery to different regions of the central nervous system. | recombinant adeno-associated virus 2 (raav2) has been shown to deliver genes to neurons effectively in the brain, retina, and spinal cord. the characterization of new aav serotypes has revealed that they have different patterns of transduction in diverse tissues. we have investigated the tropism and transduction frequency in the central nervous system (cns) of three different raav vector serotypes. the vectors contained aav2 terminal repeats flanking a green fluorescent protein expression casset ... | 2004 | 15294177 |
| infectious titer assay for adeno-associated virus vectors with sensitivity sufficient to detect single infectious events. | a highly sensitive assay for determination of infectious titers of recombinant adeno-associated virus (aav) by limiting dilution analysis is described. this assay is capable of detecting single infectious events and can therefore provide an absolute rather than relative measure of infectivity. the assay utilizes a hela-derived aav2 rep/cap-expressing cell line, d7-4, grown in 96-well plates and infected with replicate 10-fold serial dilutions of aav2 vectors in the presence of adenovirus type 5. ... | 2004 | 15298029 |
| restriction of neuroblastoma angiogenesis and growth by interferon-alpha/beta. | we tested the hypothesis that the antiangiogenic activity of the type i interferons (ifns), could affect tumor engraftment and growth in murine xenograft models of neuroblastoma. | 2004 | 15300178 |
| attenuation of dengue virus infection by adeno-associated virus-mediated sirna delivery. | background: the need for safe and effective treatment of dengue virus (den), a class a agent that causes dengue hemorrhagic fever/dengue shock syndrome, has been a critical global priority. an effective vaccine for den is not yet available. in this study the possibility of attenuating den infection using adeno-associated virus (aav)-encoded short interfering rnas (sirna) was examined in vero cells and human dendritic cells (dcs). methods: a cassette encoding sirna targeted to a 3' untranslated s ... | 2004 | 15301687 |
| structure of adeno-associated virus type 2 rep40-adp complex: insight into nucleotide recognition and catalysis by superfamily 3 helicases. | we have determined the structure of adeno-associated virus type 2 (aav2) rep40 to 2.1-a resolution with adp bound at the active site. the complex crystallizes as a monomer with one adp molecule positioned in an unexpectedly open binding site. the nucleotide-binding pocket consists of the p-loop residues interacting with the phosphates and a loop (nucleoside-binding loop) that emanates from the last strand of the central beta-sheet and interacts with the sugar and base. as a result of the open na ... | 2004 | 15310852 |
| expression of vascular endothelial growth factor (vegf) in human osteosarcoma cells transfected with adeno-associated virus-antisense vegf. | the expression of protein vascular endothelial growth factor (vegf) in osteosarcoma cells transfected with adeno-associated virus (raav)-antisense vegf was studied to provide the foundation of osteosarcoma treatment through antivascularization. the raav-antisense vegf at different doses (0, 20, 50, 100, 200, 240 microl) was transfected into osteosarcoma mg-63 cell. the cells and culture supernatants were collected before and after tansfection. the expression of vegf protein was detected by using ... | 2004 | 15315348 |
| therapeutic levels of factor ix expression using a muscle-specific promoter and adeno-associated virus serotype 1 vector. | extensive studies in animal models of the x-linked bleeding disorder hemophilia b (deficiency in functional coagulation factor ix, f.ix) have shown that muscle-directed adeno-associated (aav)-mediated f.ix gene transfer can be used to treat this disease. however, large vector doses of aav-2 vector are required for therapeutic levels of expression, and the number of vector doses that can be injected per intramuscular site is limited. several studies have shown that some of these limitations can b ... | 2004 | 15319035 |
| hiv-1 integration sites are flanked by potential mars that alone can act as promoters. | matrix attachment regions (mars) are cis regulatory elements that modulate gene expression in a tissue and cell stage specific manner. recent reports show that viral integration within the genome takes place at nonrandom active genes. we have checked for the presence of mars in the vicinity of the reported 524 hiv-1 integration sites. our studies show that in 92.5% cases, mars flank the integration sites. similarly, for adeno-associated virus, two potential mars were present next to the integrat ... | 2004 | 15325282 |
| widespread correction of lysosomal storage following intrahepatic injection of a recombinant adeno-associated virus in the adult mps vii mouse. | mucopolysaccharidosis type vii is a lysosomal storage disease caused by deficiency of the acid hydrolase beta-glucuronidase. mps vii mice develop progressive lysosomal accumulation of glycosaminoglycans within multiple organs, including the brain. using this animal model, we investigated whether gene transfer mediated by a recombinant adeno-associated virus (raav) type 2 vector is capable of reversing the progression of storage in adult mice. we engineered an raav2 vector to carry the murine bet ... | 2004 | 15336648 |
| differential myocardial gene delivery by recombinant serotype-specific adeno-associated viral vectors. | recombinant cross-packaging of adeno-associated virus (aav) genome of one serotype into other aav serotypes has the potential to optimize tissue-specific gene transduction and expression in the heart. to evaluate the role of aav1 to 5 virion shells on aav2 transgene transduction, we constructed hybrid vectors in which each serotype capsid coding domain was cloned into a common vector backbone containing aav2 replication genes. constructs were tested for expression in: (1) adult murine heart in v ... | 2004 | 15336660 |
| [generation of human recombinant antibody fab fragment and its igg to adeno-associated virus type ii from phage display library]. | to acquire the recombinant human monoclonal antibodies and igg to adeno-associated virus type 2 (aavs-2). | 2003 | 15340567 |
| development of packaging cell lines for generation of adeno-associated virus vectors by lentiviral gene transfer of trans-complementary components. | adeno-associated virus (aav) vector system has several useful advantages with regard to in vitro and in vivo gene transfer. however, their usages have been limited by cumbersome and labor-intensive vector production in the traditional method. to overcome limitations in aav production, in this report, we explored the possibility of generating aav packaging cell line, 293t r/c.va.e2a.e4. cells, by using lentivirus-mediated transduction of rep/cap gene of aav-2, va rna, e2a, and e4 genes of ad5 int ... | 2004 | 15347316 |
| [immortalization of human embryonic cervical epithelial cells induced by e6, e7 genes of human papillomavirus 16]. | to establish an immortalized cell line derived from the embryonic cervical epithelium by infection with the recombinant adeno-associated virus (raav) containing human papillomavirus (hpv)16 e6, e7, and to study the biological features of cervical cancer cell line. | 2004 | 15347475 |
| characterization of a nuclear localization signal in the c-terminus of the adeno-associated virus rep68/78 proteins. | adeno-associated virus (aav) replicates in the nucleus of infected cells, and therefore multiple nuclear import events are required for productive infection. we analyzed nuclear import of the viral rep proteins and characterized a nuclear localization signal (nls) in the c-terminus. we demonstrate that basic residues in this region constitute an nls that is transferable and mediates interaction with the nuclear import receptor importin alpha in vitro. mutant rep proteins are predominantly cytopl ... | 2004 | 15351208 |
| sequence analysis, viral rescue from infectious clones and generation of recombinant virions of the avian adeno-associated virus. | aiming at the generation of a viral-vectored system for gene delivery and vaccination in poultry, the entire genomes of the vr-865 and da-1 strains of the avian adeno-associated virus have been cloned and sequenced. sequence analysis of the clones showed that the genomic distribution of the structural and non-structural protein-coding genes of these viruses is conserved and in agreement with what has been previously described for the primate adeno-associated viruses. amino acid differences betwe ... | 2004 | 15351493 |
| differential raav2 transduction efficiencies and insulin secretion profiles in pure and co-culture models of human enteroendocrine l-cells and enterocytes. | cell-based therapies for treating insulin-dependent diabetes (idd) can provide a more physiologic regulation of blood glucose levels in a less invasive fashion than insulin injections. previously, we developed an engineered human enteroendocrine l-cell model for regulated insulin release via recombinant adeno-associated virus serotype 2, or raav2, transduction. the aim of this study was to evaluate the efficiency and selectivity of raav2-mediated insulin gene delivery to enteroendocrine l-cells ... | 2004 | 15352073 |
| functional characterization of a recombinant adeno-associated virus 5-pseudotyped cystic fibrosis transmembrane conductance regulator vector. | despite extensive experience with recombinant adeno-associated virus (raav) 2 vectors in the lung, gene expression has been low in the context of cystic fibrosis (cf) gene therapy, where the large size of the cystic fibrosis transmembrane conductance regulator (cftr) coding sequence has prompted the use of compact endogenous promoter elements. we evaluated the possibility that gene expression from recombinant adeno-associated virus (raav) could be improved by using alternate aav capsid serotypes ... | 2004 | 15353038 |
| augmentation of antitumor activity of a recombinant adeno-associated virus carcinoembryonic antigen vaccine with plasmid adjuvant. | recombinant adeno-associated virus 2 (raav) vectors have been successfully used for sustained expression of therapeutic genes. the potential of using raav as a cancer vaccine vector and the impact of a bacterial plasmid adjuvant on this activity were investigated. c57bl/6 mice received a single intramuscular injection of raav expressing the human tumor-associated antigen, carcinoembryonic antigen (cea). three weeks later, when cea expression was optimal, a bacterial plasmid containing methylated ... | 2004 | 15353040 |
| trans-splicing adeno-associated viral vector-mediated gene therapy is limited by the accumulation of spliced mrna but not by dual vector coinfection efficiency. | therapeutic application of recombinant adeno-associated virus (aav) has been limited by its small carrying capacity. to overcome this limitation trans-splicing vectors were developed recently. however, the transduction efficiency of trans-splicing vectors is considerably lower than that of a single intact vector in skeletal muscle. to improve trans-splicing vectors for skeletal muscle gene therapy, we examined whether coinfection efficiency is a rate-limiting factor in the mdx mouse, a model for ... | 2004 | 15353044 |
| long-term correction of murine lipoprotein lipase deficiency with aav1-mediated gene transfer of the naturally occurring lpl(s447x) beneficial mutation. | human lipoprotein lipase (lpl) deficiency causes profound hypertriglyceridemia and life-threatening pancreatitis. we recently developed an adult murine model for lpl deficiency: lpl -/- mice display grossly elevated plasma triglyceride (tg) levels (>200-fold) and very low high-density lipoprotein cholesterol (hdl-c < 10% of normal). we used this animal model to test the efficacy of adeno-associated virus-mediated expression of hlpl(s447x) (aav1-lpl(s447x)) in muscle for the treatment of lpl defi ... | 2004 | 15353045 |
| antiangiogenic cancer gene therapy by adeno-associated virus 2-mediated stable expression of the soluble fms-like tyrosine kinase-1 receptor. | antiangiogenic gene transfer has the potential to be more efficacious than protein-based therapies or pharmacotherapies for the control of solid tumor growth, invasion and metastasis. for a sustained antiangiogenic effect, a vector capable of long-term expression without vector-associated immunity or toxicity is advantageous. the present study evaluated the potential of a recombinant adeno-associated virus-2 (raav) encoding the human soluble fms-like tyrosine kinase receptor 1 (sflt-1), which fu ... | 2005 | 15359287 |
| residues within the b' motif are critical for dna binding by the superfamily 3 helicase rep40 of adeno-associated virus type 2. | we have recently published the crystal structure of the adeno-associated virus type 2 superfamily 3 (sf3) helicase rep40. although based on its biochemical properties it is unlikely that rep40 plays a central role as a replicative helicase the involvement of this motor protein in dna packaging has recently been demonstrated. here we focused our attention on residues that fall within and adjacent to the b' motif of sf3 helicases that directly interact with single-stranded dna during translocation ... | 2004 | 15371437 |
| feasibility of gene therapy in gaucher disease using an adeno-associated virus vector. | gaucher disease, one of the common lysosomal storage disorders, is caused by a deficiency of glucocerebrosidase (gc). we investigated gene transfer using recombinant adeno-associated viral (raav) vectors containing human gc cdna driven by the human elongation factor 1-alpha promoter. this raav vector mediated efficient expression of human gc in human gaucher fibroblasts. gc activities were increased from 2.8 to 3.4 times in normal fibroblast and from 1.9 to 4.6 times in gaucher fibroblasts, and ... | 2004 | 15372321 |
| analysis of the production efficiency and titration of various recombinant adeno-associated viruses. | recombinant adeno-associated virus type 2 (raav2) viral vector, a non-pathogenic human parvovirus, has recently emerged as a gene transfer vehicle for cancer gene therapy. to utilize raav2 properly and safely while carrying out preclinical and clinical studies, it is crucial to exactly titer the virus. we therefore compared biological infectious raav2 titers with physical titers of raav2 vectors encoding various transgenes with different sized viral genomes. biological raav2 infectivity was assa ... | 2004 | 15375497 |
| purification of recombinant adeno-associated virus type 8 vectors by ion exchange chromatography generates clinical grade vector stock. | recombinant vectors based on the recently isolated aav serotype 8 (raav-8) shows great promise for gene therapy, particularly for disorders affecting the liver. transition of this vector system to the clinic, however, is limited by the lack of an efficient scaleable purification method. in this report, we describe a simple method for purification of raav-8 vector particles based on ion exchange chromatography that generates vector stocks with greater than 90% purity. the average yield of purifie ... | 2004 | 15381358 |
| 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 |
| progress in the use of adeno-associated viral vectors for gene therapy. | the development of safe and efficient gene transfer vectors is crucial for the success of gene therapy trials. a viral vector system promising to meet these requirements is based on the apathogenic adeno-associated virus (aav-2), a member of the parvovirus family. the advantages of this vector system is the stability of the viral capsid, the low immunogenicity, the ability to transduce both dividing and non-dividing cells, the potential to integrate site specifically and to achieve long-term gen ... | 2004 | 15388988 |
| recombinant adeno-associated virus 2-mediated transfer of the human superoxide-dismutase gene does not confer radioresistance on hela cervical carcinoma cells. | the success rate of any therapeutic approach depends on the therapeutic window, which can be increased by either raising the resistance of the normal tissue without protecting the tumor cells or by sensitizing the tumor cells but not the normal cells. two promising candidate genes for normal tissue protection against radiation-induced damage may be the copper-zinc (cuznsod) and manganese superoxide-dismutase genes (mnsod). the recombinant adeno-associated virus 2 (raav-2) offers attractive advan ... | 2004 | 15450734 |
| site-specific integration of functional transgenes into the human genome by adeno/aav hybrid vectors. | uncontrolled insertion of gene transfer vectors into the human genome is raising significant safety concerns for their clinical use. the wild-type adeno-associated virus (aav) can insert its genome at a specific site in human chromosome 19 (aavs1) through the activity of a specific replicase/integrase protein (rep) binding both the aavs1 and the viral inverted terminal repeats (itrs). aav-derived vectors, however, do not carry the rep gene and cannot maintain site-specific integration properties ... | 2004 | 15451450 |
| efficient transduction of skeletal muscle using vectors based on adeno-associated virus serotype 6. | vectors based on recombinant adeno-associated viruses (raav) have emerged as tools of choice for gene transfer to skeletal muscle. raav vectors demonstrate efficient, safe, and stable transduction. multiple serotypes of aav exist, but vectors based on serotype 2 (raav2) are the most thoroughly characterized and frequently employed. here, we characterize transduction of the skeletal musculature using raav vectors pseudotyped with serotype 6 capsid proteins (raav6). we demonstrate that raav6 vecto ... | 2004 | 15451451 |
| photoreceptor protection by iris pigment epithelial transplantation transduced with aav-mediated brain-derived neurotrophic factor gene. | to determine whether subretinal transplantation of iris pigment epithelial (ipe) cells transduced with the adeno-associated virus (aav2)-mediated brain-derived neurotrophic factor (bdnf) gene can protect photoreceptors against phototoxicity. | 2004 | 15452082 |
| splice junction map of simian parvovirus transcripts. | the transcription map of simian parvovirus (spv), an erythrovirus similar to parvovirus b19, was investigated. rna was extracted from tissues of experimentally infected cynomolgus macaques and subjected to reverse transcription-pcr with spv-specific primers. the pcr products were cloned and sequenced to identify splice junctions. a total of 14 distinct sequences were identified as putative partial transcripts. of these, 13 were spliced; a single unspliced transcript putatively encoded ns1. seque ... | 2004 | 15452211 |
| herpes simplex virus type 1 icp0 protein mediates activation of adeno-associated virus type 2 rep gene expression from a latent integrated form. | adeno-associated virus type 2 (aav-2) is a human parvovirus that requires the presence of a helper virus, such as the herpes simplex virus type 1 (hsv-1) to accomplish a complete productive cycle. in the absence of helper virus, aav-2 can establish a latent infection that is characterized by the absence of expression of viral genes. so far, four hsv-1 early genes, ul5/8/52 (helicase primase complex) and ul29 (single-stranded dna-binding protein), were defined as sufficient for aav replication wh ... | 2004 | 15452218 |
| recombinant aav-mediated gene transfer to the retina: gene therapy perspectives. | retinal degenerative diseases such as retinal macular degeneration and retinitis pigmentosa constitute a broad group of diseases that all share one critical feature, the progressive apoptotic loss of cells in the retina. there is currently no effective treatment available by which the course of these disorders can be modified, and visual dysfunction often progresses to total blindness. gene therapy represents an attractive approach to treating retinal degeneration because the eye is easily acces ... | 2004 | 15454954 |
| isolation of an adenovirus and an adeno-associated virus from goat kids with enteritis. | a dairy goat operation in minnesota experienced a sudden, markedly increased mortality among its neonatal goats. approximately 60 of 130 kids (46%) died. the animals had diarrhea and dyspnea of 1-2 days duration before death. necropsy of 4 goat kids revealed marked, acute, catarrhal enteritis and fibrinous pleuropneumonia. mannheimia haemolytica was isolated from the lungs. basophilic inclusion bodies filling the entire nucleus were present in enterocytes of the ileum of 3 goats. adenoviral part ... | 2004 | 15460334 |
| 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 |
| susceptibility of mesothelioma cell lines to adeno-associated virus 2 vector-based suicide gene therapy. | although great efforts have been made to improve conventional therapy for diffuse malignant pleural mesothelioma, the median survival time of the patients after appearance of clinical symptoms remains poor. due to confinement of the primary tumor to the pleural space, locoregional approaches are attractive strategies to improve the clinical outcome. in this context locoregional gene therapy using the recombinant adeno-associated virus 2 (raav-2) may be a new approach. vectors were constructed co ... | 2004 | 15474666 |
| 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 |
| large-scale production, purification and crystallization of wild-type adeno-associated virus-2. | adeno-associated virus-2 (aav-2) has long been recognized as a potential vector for human gene therapy. although much progress has been made in the molecular virology of aav-2, structural studies of aav-2 have been hampered by the low efficiency of virus production in culture, the low purity of preparations, and the low solubility of pure virus particles in solution. methods of larger scale aav-2 production have been developed through adaptation to suspension culture and re-optimization of the t ... | 2004 | 15488616 |
| non-viral vectors in cystic fibrosis gene therapy: progress and challenges. | although the viability of cystic fibrosis (cf) gene transfer to airway epithelium has been demonstrated in vitro and in animal models, so far none of the clinical investigations using adenovirus, adeno-associated virus, lentivirus, cationic lipids or polymers has shown a persistent correction of the ion transport defects that occur in cf. despite disappointing results, these studies have shown that non-viral vectors could represent a viable alternative for gene therapy in cf airway epithelium. t ... | 2004 | 15491803 |