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adeno-associated virus-mediated human il-10 gene transfer suppresses the development of experimental autoimmune orchitis.testicular germ cell-induced autoimmune orchitis is characterized by inflammatory cell infiltration followed by disturbance of spermatogenesis. experimental autoimmune orchitis (eao) is an animal model for human immunological male infertility; delayed-type hypersensitivity (dth) response plays a key role in its induction. interleukin-10 (il-10) is a regulatory cytokine that is critical in preventing organ-specific autoimmune inflammation. to determine the effects on eao of human il-10 (hil-10) g ...200515920464
[adeno-associated virus-mediated expression of human endostatin and its biological activity in vitro].to construct the recombinant adeno-associated viral vector containing human endostatin gene (raav-hendo) and observe the biological activity of the expressed human endostatin in vitro.200515958300
adeno-associated virus-vectored gene therapy for retinal disease.recombinant adeno-associated viral (aav) vectors have become powerful gene delivery tools for the treatment of retinal degeneration in a variety of animal models that mimic corresponding human diseases. aav vectors possess a number of features that render them ideally suited for retinal gene therapy, including a lack of pathogenicity, minimal immunogenicity, and the ability to transduce postmitotic cells in a stable and efficient manner. in the sheltered environment of the retina, aav vectors ar ...200515960597
gene therapy for haemophilia.progress toward the development of a gene therapy protocol for the treatment of haemophilia has been substantial. recent achievements include high level clotting factor expression in mice, dogs, and monkeys as well as phenotypic correction in both mouse and canine models of haemophilia. studies using adenoviral vectors have contributed to much of the recent success. however, the repertoire of gene transfer vehicles being applied to the development of gene therapy strategies for haemophilia has e ...199715989572
adeno-associated virus mediated interferon-gamma inhibits the progression of hepatic fibrosis in vitro and in vivo.to investigate the effects of adeno-associated virus (aav) mediated expression of human interferon-gamma for gene therapy in experimental hepatic fibrosis in vitro and in vivo.200515996030
adeno-associated virus-mediated bone morphogenetic protein-7 gene transfer induces c2c12 cell differentiation into osteoblast lineage cells.to investigate the effects of bone morphogenetic protein-7 (bmp7)-expressing recombinant adeno-associated virus (aav) vector on the differentiation of c2c12 cells.200516038629
improved tissue repair in articular cartilage defects in vivo by raav-mediated overexpression of human fibroblast growth factor 2.therapeutic gene transfer into articular cartilage is a potential means to stimulate reparative activities in tissue lesions. we previously demonstrated that direct application of recombinant adeno-associated virus (raav) vectors to articular chondrocytes in their native matrix in situ as well as sites of tissue damage allowed for efficient and sustained reporter gene expression. here we test the hypothesis that raav-mediated overexpression of fibroblast growth factor 2 (fgf-2), one candidate fo ...200516043094
partial correction of sensitivity to oxidant stress in friedreich ataxia patient fibroblasts by frataxin-encoding adeno-associated virus and lentivirus vectors.peripheral nervous system (pns) sensory neurons are directly involved in the pathophysiology of a number of debilitating inherited and acquired neurological conditions. the lack of effective treatments for many such conditions provides a strong rationale for exploring novel therapeutic approaches, including gene therapy. friedreich ataxia (frda), a sensory neuropathy, is a progressive neurodegenerative disease associated with a loss of large sensory neurons from the dorsal root ganglia. because ...200516076253
targeting viral-mediated transduction to the lung airway epithelium with the anti-inflammatory cationic lipid dexamethasone-spermine.we formulated adenovirus (adv) vectors with cationic steroid liposomes containing dexamethasone-spermine (ds)/dioleoylphosphatidylethanolamine (dope) in an effort to overcome the lack of apically expressed adv vector receptors on airway epithelial cells and to reduce the inflammation associated with adv vector exposure. an adv vector (1 to 2.5 x 10(11) genome copies) expressing human placental alkaline phosphatase or beta-galactosidase (lacz) was delivered alone or complexed with ds/dope, dc-cho ...200516099413
neuroprotective adeno-associated virus bcl-xl gene transfer in models of motor neuron disease.recent work implicates excitotoxicity-induced apoptosis as the mechanism triggering motor neuron death in amyotrophic lateral sclerosis (als). our laboratory has previously utilized glutamate excitotoxicity in vitro to study this process. the present experiment tests whether overexpression of the gene for bcl-xl can inhibit excitotoxicity in this model system. to track bcl-xl expression, the gene for green fluorescent protein (gfp) was inserted in-frame, upstream of the bcl-xl gene. the gfp-bcl- ...200516116646
superior neovascularization and muscle regeneration in ischemic skeletal muscles following vegf gene transfer by raav1 pseudotyped vectors.recombinant adeno-associated virus serotype 2 (raav2) vector has been widely employed for gene therapy. recent progress suggests that the new serotypes of aav showed a better performance than did aav2 in normal tissues. here, we evaluate the potential role of human vascular endothelial growth factor (vegf) gene transfer using raav vector pseudotyped with serotype 1 capsid proteins (raav1) in the treatment of muscle ischemia. in ischemic skeletal muscles, the raav1-lacz vector allowed higher leve ...200516129416
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.200616144019
uniform scale-independent gene transfer to striated muscle after transvenular extravasation of vector.the muscular dystrophies exemplify a class of systemic disorders for which widespread protein replacement in situ is essential for treatment of the underlying genetic disorder. somatic gene therapy will require efficient, scale-independent transport of dna-containing macromolecular complexes too large to cross the continuous endothelia under physiological conditions. previous studies in large-animal models have revealed a trade-off between the efficiency of gene transfer and the inherent safety ...200516157771
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 ...200616162872
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 ...200616195782
delivery of human acetylcholinesterase by adeno-associated virus to the acetylcholinesterase knockout mouse.the purpose of this work was to develop a gene delivery system that expressed acetylcholinesterase (ache) for prolonged periods. an adeno-associated virus (aav) expressing human ache was constructed by co-transfecting three plasmids into hek 293t cells. the purified vector expressed 0.17 microg ache per 1 million viral particles in culture medium in 23 h, or 0.8 u/ml. the aav/hache was injected into muscle of adult ache knockout mice and into the brains of 3-6 week old ache knockout mice. intram ...200516243306
gene therapy for lipoprotein lipase deficiency: working toward clinical application.lipoprotein lipase (lpl) deficiency causes hypertriglyceridemia and recurrent, potentially life-threatening pancreatitis. there currently is no adequate treatment for this disease. previously, we showed that intramuscular administration of an adeno-associated virus serotype 1 (aav1) vector encoding the human lpl(s447x) variant cdna (aav1-lpl(s447x)) normalized the dyslipidemia of lpl-/- mice for more than 1 year. in preparation for a clinical trial, we evaluated the safety and biodistribution of ...200516259561
safety and efficacy of aav-mediated calpain 3 gene transfer in a mouse model of limb-girdle muscular dystrophy type 2a.calpainopathy (limb-girdle muscular dystrophy type 2a, lgmd2a) is a recessive muscular disorder caused by deficiency in the calcium-dependent cysteine protease calpain 3. to date, no treatment exists for this disease. we evaluated the potential of recombinant adeno-associated virus (raav) vectors for gene therapy in a murine model for lgmd2a. to drive the expression of calpain 3, we used raav2/1 pseudotyped vectors and muscle-specific promoters to avoid calpain 3 cell toxicity. we report efficie ...200616290124
intracerebral adeno-associated virus-mediated gene transfer in rapidly progressive forms of metachromatic leukodystrophy.metachromatic leukodystrophy (mld) is a neurodegenerative lysosomal disease caused by a defect of the enzyme arylsulfatase a (arsa) that disrupts the degradation of sulfatides (sulf) in neurons and glial cells. therapy for mld requires active production of arsa in the brain to prevent demyelination and neuronal damage, and efficient delivery of arsa to act faster than disease progression, particularly in the rapidly progressive late infantile form. we used an adeno-associated virus serotype 5 (a ...200616311251
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 ...200616319949
analysis of adeno-associated virus and hpv interaction.it is slowly becoming accepted that adeno-associated virus (aav) is another significant factor involved in cervical carcinogenesis. however, unlike human papillomavirus (hpv), which is positively associated with cervical cancer, aav is negatively associated with this cancer. this negative association appears to be through a direct and complex bi-directional interaction between aav and hpv. essentially all assays used for studying hpv can be used for studying the aav-hpv interaction. this is beca ...200516350413
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 ...200616407771
development of anticancer gene vaccine interact with human papillomavirus oncoprotein inhibition.adeno-associated virus (aav) rep 78 protein is known to inhibit the promoter site of several oncogenes and viral genes, including the human papillomavirus (hpv) type 16 e6 transforming genes. the biochemical studies of rep 78 have been reported, but the effects of rep 78 gene-mediated inhibition of hpv 16 e6 promoter activity on the various human cervical carcinoma cells have not been characterized. pegfp-n1 vector, cloned by aav-mediated rep 78, is transfected into cervical carcinoma cells. tra ...200616445644
intracranial delivery of cln2 reduces brain pathology in a mouse model of classical late infantile neuronal ceroid lipofuscinosis.classical late infantile neuronal ceroid lipofuscinosis (clincl) is a lysosomal storage disorder caused by mutations in cln2, which encodes lysosomal tripeptidyl peptidase i (tpp1). lack of tpp1 results in accumulation of autofluorescent storage material and curvilinear bodies in cells throughout the cns, leading to progressive neurodegeneration and death typically in childhood. in this study, we injected adeno-associated virus (aav) vectors containing the human cln2 cdna into the brains of cln2 ...200616452657
[expression of coagulation factor ix in human cd34 + hematopoietic stem cells by adeno-associated virus 2].to investigate the expression of human coagulation factor ix (hfix) gene in human umbilical cord blood (cb) cd34+ cells which was transfected with recombinant adeno-associated virus 2 (raav-2).200516468329
freeze-thaw increases adeno-associated virus transduction of cells.a combination of gene and cell-based therapies may provide significant advantages over existing treatments in terms of their effectiveness. however, long-term efficient gene delivery has been difficult to achieve in many cell types, including endothelial cells. we developed a freeze-thaw technique which significantly increases the transduction efficiency of recombinant adeno-associated virus vectors in human aortic endothelial cells (23-fold) and in human renal proximal tubular epithelial cells ...200616510845
a 16bp rep binding element is sufficient for mediating rep-dependent integration into aavs1.adeno-associated virus (aav) is a non-pathogenic virus and the only known eukaryotic virus capable of targeting human chromosome 19 for integration at a well-characterized aavs1 site. its site-specific integration is mediated by rep68 and rep78, viral proteins that bind to both the viral genome and aavs1 site on ch19 through a specific rep-binding element (rbe) located in both the viral genome and aavs1. there are three rbes in the aav genome: two identical ones in both inverted terminal repeats ...200616516232
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, ...200616527742
recombinant aav-mediated hsvtk gene transfer with direct intratumoral injections and tet-on regulation for implanted human breast cancer.hsvtk/ganciclovir (gcv) gene therapy has been extensively studied in tumors and relies largely on the gene expression of hsvtk. most studies, however, have failed to demonstrate any significant benefit of a controlled gene expression strategy in cancer treatment. the tet-on system is commonly used to regulate gene expression following dox induction. we have evaluated the antitumor effect of hsvtk/ganciclovir gene therapy under tet-on regulation by means of adeno-associated virus-2 (aav-2)-mediat ...200616539746
adeno-associated virus-mediated transduction of vegf165 improves cardiac tissue viability and functional recovery after permanent coronary occlusion in conscious dogs.we have previously shown that vegf165 gene delivery into ischemic skeletal muscle exerts not only proangiogenic, but also remarkable antiapoptotic and proregenerative activity. the aim of this study was to determine whether recombinant adeno-associated virus (raav)-mediated gene delivery of vegf165 into cardiac muscle, during acute myocardial infarction, exerts a protective effect to promote long-term functional recovery. acute infarction of the anterior lv wall was induced in 12 chronically ins ...200616543500
c-terminal-truncated microdystrophin recruits dystrobrevin and syntrophin to the dystrophin-associated glycoprotein complex and reduces muscular dystrophy in symptomatic utrophin/dystrophin double-knockout mice.c-terminal-truncated (deltac) microdystrophin is being developed for duchenne muscular dystrophy gene therapy. encouraging results have been achieved in the mdx mouse model. unfortunately, mdx mice do not display the same phenotype as human patients. evaluating deltac microdystrophin in a symptomatic model will be of significant relevance to human trials. utrophin/dystrophin double-knockout (u-dko) mice were developed to model severe dystrophic changes in human patients. in this study we evaluat ...200616563874
prevalence of neutralizing antibodies against adeno-associated virus (aav) types 2, 5, and 6 in cystic fibrosis and normal populations: implications for gene therapy using aav vectors.adeno-associated virus (aav) vectors are promising candidates for gene therapy directed to the lungs, in particular for treatment of cystic fibrosis (cf). in animal models of lung gene transfer, neutralizing antibodies in serum made in response to vector exposure have been associated with a partial to complete block to repeat transduction by vectors with the same capsid type, thus transduction by aav vectors might be inefficient in humans previously exposed to the same aav type. aav type 2 (aav2 ...200616610931
adeno-associated virus-mediated expression of apolipoprotein (a) kringles suppresses hepatocellular carcinoma growth in mice.hepatocellular carcinoma (hcc) constitutes more than 90% of all primary liver cancers. hcc is a hypervascular tumor that develops from dedifferentiation of small avascular hcc and is therefore a good target for anti-angiogenic gene therapy. recent studies have identified apolipoprotein(a) [apo(a)] kringles lk68 and lk8 (lks) as having a potential antiangiogenic and anti-tumor activity, and the current study evaluates the therapeutic potential of gene therapy with recombinant adeno-associated vir ...200616628632
membrane-associated heparan sulfate is not required for raav-2 infection of human respiratory epithelia.adeno-associated virus type 2 (aav-2) attachment and internalization is thought to be mediated by host cell membrane-associated heparan sulfate proteoglycans (hspg). lack of hspg on the apical membrane of respiratory epithelial cells has been identified as a reason for inefficient raav-2 infection in pulmonary applications in-vivo. the aim of this investigation was to determine the necessity of cell membrane hspg for efficient infection by raav-2.200616630361
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 ...200616641284
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 ...200616644289
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.200616685745
fatality in mice due to oversaturation of cellular microrna/short hairpin rna pathways.rna interference (rnai) is a universal and evolutionarily conserved phenomenon of post-transcriptional gene silencing by means of sequence-specific mrna degradation, triggered by small double-stranded rnas. because this mechanism can be efficiently induced in vivo by expressing target-complementary short hairpin rna (shrna) from non-viral and viral vectors, rnai is attractive for functional genomics and human therapeutics. here we systematically investigate the long-term effects of sustained hig ...200616724069
complete prevention of atherosclerosis in apoe-deficient mice by hepatic human apoe gene transfer with adeno-associated virus serotypes 7 and 8.using intravenous injection of adeno-associated viral (aav) vectors based on novel serotypes 7 and 8, we examined whether liver-specific expression of human apolipoprotein e (apoe) in apoe-deficient mice would completely prevent atherosclerosis after 1 year of sustained expression.200616763161
chimeric herpes simplex virus/adeno-associated virus amplicon vectors.chimeric or hybrid herpes simplex virus type 1/adeno-associated virus amplicon vectors combine the large transgene capacity of hsv-1 with the potential for site-specific genomic integration and stable transgene expression of aav. these chimeric vectors have been demonstrated to support transgene expression for significantly longer periods than standard hsv-1 amplicons. moreover, hsv/aav hybrid vectors can mediate integration at the aavs1 pre-integration site on human chromosome 19 at a relativel ...200616787183
chemotherapeutic agents enhance aav2-mediated gene transfer into breast cancer cells promoting cd40 ligand-based immunotherapy.supplementing conventional treatment with gene therapy to induce an immune response might be beneficial to cancer patients. in this study, we evaluated the efficiency of transduction of breast cancer cells with recombinant adeno-associated virus (raav) and effects of cytotoxic agents used in chemotherapy. furthermore, the capacity of tumor cells expressing transgenic cd40 ligand (cd40l) to stimulate dendritic cells was measured.200616794829
gene therapy for als: progress and prospects.amyotrophic lateral sclerosis (als) is a devastating disease for which there are no effective drug treatments to date. recent advances in gene therapy open up the possibility of developing an effective treatment aiming at halting or delaying the degeneration of motor neurons. viral vectors such as lentiviral vectors and adeno-associated virus can transfer genes into many different types of primary neurons from a broad range of species including man and the resulting gene expression is long-term. ...200616806843
serotype-specific detection of adeno-associated virus during laboratory preparation.adeno-associated virus (aav) is a small single-stranded dna member of the family parvoviradae with at least eight recognized human serotypes, several of which are being studied as candidate vectors for gene therapy. when multiple serotypes are handled in the same laboratory, it is critical to know the serotype of a sample with certainty. here, a rapid and reliable pcr-based method is presented for the identification of serotypes 2, 3b or 6 and for screening for cross contamination. the pcr assay ...200616815560
effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy.in a clinical study of recombinant adeno-associated virus-2 expressing human factor ix (aav2-fix), we detected 2 impediments to long-term gene transfer. first, preexisting anti-aav neutralizing antibodies (nabs) prevent vector from reaching the target tissue, and second, cd8(+) t-cell responses to hepatocyte-cell surface displayed aav-capsid-terminated fix expression after several weeks. because the vector is incapable of synthesizing viral proteins, a short course of immunosuppression, until aa ...200616868252
gene therapy for hemophilia.this review will highlight the progress achieved in the past 2 years on using gene therapy to treat hemophilia in animals and humans.200616888433
unique biologic properties of recombinant aav1 transduction in polarized human airway epithelia.the choice of adeno-associated virus serotypes for clinical applications is influenced by the animal model and model system used to evaluate various serotypes. in the present study, we sought to compare the biologic properties of raav2/1, raav2/2, and raav2/5 transduction in polarized human airway epithelia using viruses purified by a newly developed common column chromatography method. results demonstrated that apical transduction of human airway epithelia with raav2/1 was 100-fold more efficie ...200616899463
intraperitoneal gene therapy by raav provides long-term survival against epithelial ovarian cancer independently of survivin pathway.epithelial ovarian carcinoma is the leading cause of death from gynecological malignancies. owing to the lack of an effective screening method, insidious onset, and non-specific symptoms, a majority of women present with advanced stage disease. despite improvements from cytoreductive surgery and chemotherapy, recurrent disease remains a formidable challenge. in the present study, we demonstrate for the first time that stable intra-abdominal genetic transfer of endostatin and angiostatin (e+a) by ...200716943851
adeno-associated virus interactions with b23/nucleophosmin: identification of sub-nucleolar virion regions.adeno-associated virus (aav) is a human parvovirus that normally requires a helper virus such as adenovirus (ad) for replication. the four replication proteins (rep78, 68, 52 and 40) encoded by aav are pleiotropic effectors of virus integration, replication, transcription and virion assembly. using rep68 column chromatography and mass spectrometry, we have identified the nucleolar, b23/nucleophosmin (npm) protein as an rep-interacting partner. rep-npm interactions were verified by co-immunofluor ...200716959286
a helper-dependent capsid-modified adenovirus vector expressing adeno-associated virus rep78 mediates site-specific integration of a 27-kilobase transgene cassette.random integration of viral gene therapy vectors and subsequent activation or disruption of cellular genes poses safety risks. major efforts in the field are aimed toward targeting vector integration to specific sites in the host genome. the adeno-associated virus (aav) rep78 protein is able to target aav integration to a specific site on human chromosome 19, called aavs1. we studied whether this ability could be harnessed to achieve site-specific integration of a 27-kb transgene cassette into a ...200616987973
[the experimental study of biomimetic artificial cartilage fabrication in vitro and ectopic chondrogenesis in vivo].tri-dimensional poly (dl-lactic-co-glycolic acid) (plga) scaffolds were fabricated using a rapid prototyping (rp) technique and the gene of human bone morphogenetic protein 2 (hbmp-2) was transferred into rabbit bone marrow stromal cells (mscs) via recombinant adeno-associated virus vectors (raav-hbmp-2). thirty-two plga scaffolds, size (4 mm x 4 mm x 4 mm), were coated with collagen type i and equally divided into 2 groups. in group a, each scaffold was loaded with 2 x 10(4) hbmp-2 (+) mscs to ...200617002110
induction of robust immune responses against human immunodeficiency virus is supported by the inherent tropism of adeno-associated virus type 5 for dendritic cells.the ability of adeno-associated virus serotype 1 to 8 (aav1 to aav8) vectors expressing the human immunodeficiency virus type 1 (hiv-1) env gp160 (aav-hiv) to induce an immune response was evaluated in balb/c mice. the aav5 vector showed a higher tropism for both mouse and human dendritic cells (dcs) than did the aav2 vector, whereas other aav serotype vectors transduced dcs only poorly. aav1, aav5, aav7, and aav8 were more highly expressed in muscle cells than aav2. an immunogenicity study of a ...200617005662
recombinant adeno-associated virus preferentially transduces human, compared to mouse, synovium: implications for arthritis therapy.despite a number of published reports, including from our own laboratory, suggesting that adeno-associated virus (aav) transduces mouse synovium, a careful analysis demonstrated transduction predominantly of the subsynovial muscle tissue, while the synovial lining is poorly transduced. to investigate the potential of aav to transduce human synovium, three human rheumatoid arthritis (ra) and two murine collagen-induced arthritis (cia) synovial cell lines were infected with recombinant aav (raav) ...200417028800
low-dose radiation response of the p21waf1/cip1 gene promoter transduced by adeno-associated virus vector.in cancer gene therapy, restriction of antitumor transgene expression in a radiation field by use of ionizing radiation-inducible promoters is one of the promising approaches for tumor-specific gene delivery. although tumor suppressor protein p53 is induced by low doses (< 1 gy) of radiation, there have been only a few reports indicating potential utilization of a p53-target gene promoter, such as that of the p21 gene. this is mainly because the transiently transfected promoter of p53-target gen ...200617079872
short regions of sequence identity between the genomes of human and rodent parvoviruses and their respective hosts occur within host genes for the cytoskeleton, cell adhesion and wnt signalling.our understanding of the mechanism(s) of pathogenesis and persistence of vertebrate parvoviruses remains incomplete. with the recent availability of the complete genome sequences of human, rat and mouse, and the ability to search these sequences and to locate matches to exact genomic regions, further insight into the interaction of parvoviruses with their human and rodent hosts is possible. to determine the extent and nature of sequence identity between candidate parvoviruses and their respectiv ...200617098972
oncoprotein akt/pkb induces trophic effects in murine models of parkinson's disease.despite promising preclinical studies, neurotrophic factors have not yet achieved an established role in the treatment of human neurodegenerative diseases. one impediment has been the difficulty in providing these macromolecules in sufficient quantity and duration at affected sites. an alternative approach is to directly activate, by viral vector transduction, intracellular signaling pathways that mediate neurotrophic effects. we have evaluated this approach in dopamine neurons of the substantia ...200617116866
adeno-associated virus 2-mediated gene transfer: role of a cellular serine/threonine protein phosphatase in augmenting transduction efficiency.we have documented that a cellular chaperone protein, fkbp52, when phosphorylated at tyrosine and/or serine/threonine (ser/thr) residues, interacts with the d-sequence in the inverted terminal repeats of the adeno-associated virus 2 (aav) genome, inhibits the viral second-strand dna synthesis, and leads to inefficient transgene expression from recombinant aav vectors in certain cell types. we have also demonstrated that fkbp52 is dephosphorylated at tyrosine residues by t-cell protein tyrosine p ...200717122803
additional gene therapy with raav-wt-p53 enhanced the efficacy of cisplatin in human bladder cancer cells.gene therapy is defined as the treatment of an acquired or inherited disease by transfer of genetic material. the most common strategies in gene therapy of bladder cancer are corrective, inductive and cytotoxic gene therapy. mutations in the p53 tumor suppressor gene are the most common molecular genetic abnormalities in bladder cancer and p53 gene transfer in the human bladder cancer cell line by adenoviral or other vectors was demonstrated to be cytotoxic. however, so far there has been no rep ...200617135787
calculating expected lung deposition of aerosolized administration of aav vector in human clinical studies.cystic fibrosis is an autosomal recessive disease affecting approximately 1 in 2500 live births. introducing the cdna that codes for normal cystic fibrosis transmembrane conductance regulator (cftr) to the small airways of the lung could result in restoring the cftr function. a number of vectors for lung gene therapy have been tried and adeno-associated virus (aav) vectors offer promise. the vector is delivered to the lung using a breath-actuated jet nebulizer. the purpose of this project was to ...200717154340
phenotypic correction of alpha-sarcoglycan deficiency by intra-arterial injection of a muscle-specific serotype 1 raav vector.alpha-sarcoglycanopathy (limb-girdle muscular dystrophy type 2d, lgmd2d) is a recessive muscular disorder caused by deficiency in alpha-sarcoglycan, a transmembrane protein part of the dystrophin-associated complex. to date, no treatment exists for this disease. we constructed recombinant pseudotype-1 adeno-associated virus (raav) vectors expressing the human alpha-sarcoglycan cdna from a ubiquitous or a muscle-specific promoter. evidence of specific immune response leading to disappearance of t ...200717164775
phosphorylation-dependent degradation of transgenic creb protein initiated by heterodimerization.the transcription factor creb (cyclic amp response element binding protein) is implicated in diverse brain functions and represents a prospective target in gene therapy for human disorders. however, the transgenic expression and stability of exogenously expressed creb within the cell remains poorly characterized. here we found that transient expression of a creb dominant interfering mutant a-creb or the inducible camp early repressor, icer, led to the dramatic decrease of exogenously co-expresse ...200717169345
impact of vegf expression on the physiological characteristics of clonal cell lines.vascular endothelial growth factor (vegf) plays a crucial role in tumor angiogenesis and growth in most solid neoplasia.200617203773
sumf1 enhances sulfatase activities in vivo in five sulfatase deficiencies.sulfatases are enzymes that hydrolyse a diverse range of sulfate esters. deficiency of lysosomal sulfatases leads to human diseases characterized by the accumulation of either gags (glycosaminoglycans) or sulfolipids. the catalytic activity of sulfatases resides in a unique formylglycine residue in their active site generated by the post-translational modification of a highly conserved cysteine residue. this modification is performed by sumf1 (sulfatase-modifying factor 1), which is an essential ...200717206939
pre-existing aav capsid-specific cd8+ t cells are unable to eliminate aav-transduced hepatocytes.the goal of these studies was to test whether adeno-associated virus (aav) capsid-specific cd8(+) t cells cause loss of hepatic aav-mediated gene expression in experimental animals. mice immunized with adenoviral vectors expressing aav capsid or with aav vectors developed cd8(+) t cells in blood, lymphatic tissues, and liver to epitopes shared between aav2 and aav8, and serotype-specific neutralizing antibodies. at the height of the t cells' effector phase, mice were infused with a heterologous ...200717245353
gangliosides, ab1 and ab2 antibodies iii. the idiotype of anti-ganglioside mab p3 is immunogenic in a t cell-dependent manner.p3 mab is an igm monoclonal antibody specific for n-glycolyl-containing gangliosides. the immunogenicity of the p3 idiotype has been previously described by immunizing syngeneic balb/c mice with the purified murine igm or the mouse-human chimeric igg antibody. in the present work we study the antibody response against the idiotype of p3 mab through immunization with dna. we used small immune proteins (sip) consisting on the idiotype in the scfv format, covalently linked to gamma1ch3, the self-di ...200717316805
self-complementary recombinant adeno-associated viral vectors: packaging capacity and the role of rep proteins in vector purity.self-complementary adeno-associated viral (scaav) vectors bypass the requirement for viral second-strand dna synthesis, but the packaging capacity of these vectors ( approximately 2.4 kb) is significantly smaller than that of conventional aav vectors ( approximately 4.8 kb). we constructed human recombinant green fluorescent protein (hrgfp) expression cassettes ranging from 2.3 to 4.1 kb. each vector was biologically active, but the transduction efficiency of vectors containing <3.3-kb genomes w ...200717328683
striatal delivery of cere-120, an aav2 vector encoding human neurturin, enhances activity of the dopaminergic nigrostriatal system in aged monkeys.neurturin (ntn) is a potent survival factor for midbrain dopaminergic neurons. cere-120, an adeno-associated virus type 2 (aav2) vector encoding human ntn (aav2-ntn), is currently being developed as a potential therapy for parkinson's disease. this study examined the bioactivity and safety/tolerability of aav2-ntn in the aged monkey model of nigrostriatal dopamine insufficiency. aged rhesus monkeys received unilateral injections of aav2-ntn into the caudate and putamen, with each animal therefor ...200717443702
papillary thyroid carcinoma with lymph node metastases.papillary thyroid cancer (ptc) is the most frequently occurring human thyroid cancer with good prognosis following appropriate treatment. lymph node (ln) metastases are the main way through which ptc spread cancer cells. the mechanisms underlying ptc with local invasion, ln metastases and distant metastases are not well investigated. tumor secrete cytokines, such as vascular endothelial growth factor (vegf)-c and -d bind to vegf receptors on lymphatic endothelial cells and induce proliferation ( ...200717454149
increased complexity of wild-type adeno-associated virus-chromosomal junctions as determined by analysis of unselected cellular genomes.adeno-associated virus (aav) undergoes preferential rep-mediated integration into the aavs1 region of human chromosome 19 during latent infection, at least in highly-selected cell cultures. however, integration at the level of the whole eukaryotic genome in unselected cells has not yet been monitored for aav as it has been for retro- and lentiviruses. here we have used ligation-mediated pcr (lmpcr) to monitor the formation of aav-chromosome junctions within unselected genomic dna after infection ...200717485532
re-engineering primary epithelial cells from rhesus monkey parotid glands for use in developing an artificial salivary gland.there is no satisfactory conventional treatment for patients who experience irreversible salivary gland damage after therapeutic radiation for head and neck cancer or because of sjögren's syndrome. additionally, if most parenchyma is lost, these patients also are not candidates for evolving gene transfer strategies. to help such patients, several years ago we began to develop an artificial salivary gland. in the present study, we used a non-human primate tissue source, parotid glands from rhesus ...200617518661
systemic cancer gene therapy using adeno-associated virus type 1 vector expressing mda-7/il24.melanoma differentiation-associated gene-7/interleukin-24 (mda-7/il24), selectively induces apoptosis in cancer cells without harming normal cells. it also exerts immunomodulatory and antiangiogenic effects, as well as potent antitumor bystander effects, making it an ideal candidate for a new anticancer gene therapy. here, we examined the feasibility of adeno-associated virus type 1 (aav1) vector-mediated systemic gene therapy using mda-7/il24. in vitro studies showed that medium conditioned by ...200717551500
gene therapy: the first two decades and the current state-of-the-art.the concept of gene therapy was envisioned soon after the emergence of restriction endonucleases and subcloning of mammalian genes in phage and plasmids. over the ensuing decades, vectors were developed, including nonviral methods, integrating virus vectors (gammaretrovirus and lentivirus), and non-integrating virus vectors (adenovirus, adeno-associated virus, and herpes simplex virus vectors). preclinical data demonstrated potential efficacy in a broad range of animal models of human diseases, ...200717577203
in vivo post-transcriptional gene silencing of alpha-1 antitrypsin by adeno-associated virus vectors expressing sirna.alpha-1 antitrypsin (aat) deficiency is one of the most common genetic diseases in north america, with a carrier frequency of approximately 4% in the us population. homozygosity for the most common mutation (glu342lys, pi(*)z) leads to the synthesis of a mutant protein, which accumulates and polymerizes within hepatocytes rather than being efficiently secreted. this lack of secretion causes severe serum deficiency predisposing to chronic lung disease. twelve to fifteen percent of patients with p ...200717592477
quiescent subpopulations of human cd34-positive hematopoietic stem cells are preferred targets for stable recombinant adeno-associated virus type 2 transduction.we have previously demonstrated recombinant adeno-associated viral (raav) transduction of human cd34(+) hematopoietic stem cells (hscs) capable of serial engraftment in vivo. here we evaluated the capacity of raav2 to mediate gene transfer into nondividing, quiescent, primitive cd34(+) cells subdivided on the basis of metabolic, mitotic, and phenotypic properties. results revealed that cd34(+)cd38() marrow cells are the most quiescent, exist primarily in g(0) at isolation and are the only popula ...200717638572
therapeutic approaches for prion disorders.prion diseases are lethal for both humans and animals, and affected individuals die after several months following a rapid disease progression. although researchers have attempted for decades to develop effective therapeutics for the therapy of human prion disorders, until now no efficient drug has been available on the market for transmissible spongiform encephalopathy (tse) treatment or cure. approximately 200 patients worldwide have died or suffer from variant creutzfeldt-jakob disease (cjd). ...200717678425
raav-mediated nigral human parkin over-expression partially ameliorates motor deficits via enhanced dopamine neurotransmission in a rat model of parkinson's disease.we hypothesized that over-expressing the e3 ligase, parkin, whose functional loss leads to parkinson's disease, in the nigrostriatal tract might be protective in the unilateral 6-hydroxydopamine (6-ohda) rat lesion model. recombinant adeno-associated virus (raav) encoding human parkin or green fluorescent protein (gfp) was injected into the rat substantia nigra 6 weeks prior to a four-site striatal 6-ohda lesion. vector-mediated parkin over-expression significantly ameliorated motor deficits as ...200717678648
repeated aerosolized aav-cftr for treatment of cystic fibrosis: a randomized placebo-controlled phase 2b trial.previous studies have demonstrated that delivery of a recombinant adeno-associated virus (aav) vector encoding the complete human cystic fibrosis transmembrane regulator (cftr) cdna (tgaavcf) to the nose, sinus, and lungs of subjects with cystic fibrosis (cf) was safe and well tolerated. in a small randomized, double-blind study of three doses of aerosolized tgaavcf or placebo at 30-day intervals, encouraging but non-significant trends in pulmonary function and induced sputum interleukin 8 (il-8 ...200717685853
vaccines based on novel adeno-associated virus vectors elicit aberrant cd8+ t-cell responses in mice.we recently discovered an expanded family of adeno-associated viruses (aavs) that show promise as improved gene therapy vectors. in this study we evaluated the potential of vectors based on several of these novel aavs as vaccine carriers for human immunodeficiency virus type 1 gag. studies with mice indicated that vectors based on aav type 7 (aav7), aav8, and aav9 demonstrate improved immunogenicity in terms of gag cd8(+) t-cell and gag antibody responses. the quality of these antigen-specific r ...200717715240
knock-in of oncogenic kras does not transform mouse somatic cells but triggers a transcriptional response that classifies human cancers.kras mutations are present at a high frequency in human cancers. the development of therapies targeting mutated kras requires cellular and animal preclinical models. we exploited adeno-associated virus-mediated homologous recombination to insert the kras g12d allele in the genome of mouse somatic cells. heterozygous mutant cells displayed a constitutively active kras protein, marked morphologic changes, increased proliferation and motility but were not transformed. on the contrary, mouse cells i ...200717875685
cone-specific expression using a human red opsin promoter in recombinant aav.to determine the feasibility of targeting gene expression specifically to cone photoreceptors using recombinant adeno-associated virus (raav) as the vector.200817905404
gender differences in serotype 2 adeno-associated virus biodistribution after administration to rodent salivary glands.salivary glands (sgs) have proven useful targets for clinical applications of gene therapeutics. in this toxicology and biodistribution study, which conforms to u.s. food and drug administration good laboratory practice regulations, four doses (10(7)-10(10) particles) of a serotype 2 adeno-associated viral (aav2) vector encoding human erythropoietin were directly administered to the right submandibular gland of male and female balb/c mice (n = 21 per gender dose group). control-treated (saline a ...200717939749
therapeutic silencing of mutant huntingtin with sirna attenuates striatal and cortical neuropathology and behavioral deficits.huntington's disease (hd) is a neurodegenerative disorder caused by expansion of a cag repeat in the huntingtin (htt) gene. hd is autosomal dominant and, in theory, amenable to therapeutic rna silencing. we introduced cholesterol-conjugated small interfering rna duplexes (cc-sirna) targeting human htt mrna (sirna-htt) into mouse striata that also received adeno-associated virus containing either expanded (100 cag) or wild-type (18 cag) htt cdna encoding huntingtin (htt) 1-400. adeno-associated v ...200717940007
intraparenchymal spinal cord delivery of adeno-associated virus igf-1 is protective in the sod1g93a model of als.the potent neuroprotective activities of neurotrophic factors, including insulin-like growth factor 1 (igf-1), make them promising candidates for treatment of amyotrophic lateral sclerosis (als). in an effort to maximize rate of motor neuron transduction, achieve high levels of spinal igf-1 and thus enhance therapeutic benefit, we injected an adeno-associated virus 2 (aav2)-based vector encoding human igf-1 (cere-130) into lumbar spinal cord parenchyma of sod1(g93a) mice. we observed robust and ...200717963733
immune responses to adenovirus and adeno-associated vectors used for gene therapy of brain diseases: the role of immunological synapses in understanding the cell biology of neuroimmune interactions.researchers have conducted numerous pre-clinical and clinical gene transfer studies using recombinant viral vectors derived from a wide range of pathogenic viruses such as adenovirus, adeno-associated virus, and lentivirus. as viral vectors are derived from pathogenic viruses, they have an inherent ability to induce a vector specific immune response when used in vivo. the role of the immune response against the viral vector has been implicated in the inconsistent and unpredictable translation of ...200717979681
an experimental system for the evaluation of retroviral vector design to diminish the risk for proto-oncogene activation.pathogenic activation of the lmo2 proto-oncogene by an oncoretroviral vector insertion in a clinical trial for x-linked severe combined immunodeficiency (x-scid) has prompted safety concerns. we used an adeno-associated virus vector to achieve targeted insertion of a gamma-retroviral long terminal repeat (ltr) driving a gfp expression cassette with flanking loxp sites in a human t-cell line at the precise location of vector integration in one of the patients with x-scid. the ltr-gfp cassette was ...200817991809
anti-idiotypic response in mice expressing human autoantibodies.celiac disease is an autoimmune illness characterized by intestinal mucosal injury and malabsorption precipitated by dietary exposure to gluten of some cereals. the immune response is based on both cellular and humoral components, although the former seem to be more important in the pathogenesis. the autoantibody response is directed at the enzyme tissue transglutaminase, ttg or tg2, which possibly play a role in the onset of the disease. in this study we sought to develop an animal model in whi ...200817996305
targeted integration of functional human atm cdna into genome mediated by hsv/aav hybrid amplicon vector.ataxia-telangiectasia (a-t) is an autosomal recessive disorder characterized by neurodegeneration, immunodeficiency, cancer predisposition, genome instability, and sensitivity to ionizing radiation (ir). we have previously shown that a herpes simplex virus type 1 (hsv-1) amplicon vector carrying the human ataxia-telangiectasia mutated (atm) complementary dna (cdna) is able to correct aspects of the cellular phenotype of human a-t cells in culture, and is also able to transfer the atm cdna to the ...200817998902
engineering adeno-associated virus 2 vectors for targeted gene delivery to atherosclerotic lesions.targeted delivery of biological agents to atherosclerotic plaques may provide a novel treatment and/or useful tool for imaging of atherosclerosis in vivo. however, there are no known viral vectors that possess the desired tropism. two plaque-targeting peptides, capgpsksc (cap) and cnhrymqmc (cnh) were inserted into the capsid of adeno-associated virus 2 (aav2) to assess vector retargeting. aav2-cnh produced significantly higher levels of transduction than unmodified aav2 in human, murine and rat ...200818004401
[gfp gene transfection of dendritic cells mediated by recombinated adeno-associated virus].to investigate the transfection condition of type 2 recombinant adeno-associated virus ( raav2) in human dendritic cells(dcs) which were induced from the bone marrow cd34+ hematopoietic stem /progenitor cells.200718007063
robust, persistent transgene expression in human embryonic stem cells is achieved with aavs1-targeted integration.silencing and variegated transgene expression are poorly understood problems that can interfere with gene function studies in human embryonic stem cells (hescs). we show that transgene expression (enhanced green fluorescent protein [egfp]) from random integration sites in hescs is affected by variegation and silencing, with only half of hescs expressing the transgene, which is gradually lost after withdrawal of selection and differentiation. we tested the hypothesis that a transgene integrated i ...200818024421
aav serotype 1 mediates more efficient gene transfer to pig myocardium than aav serotype 2 and plasmid.adeno-associated virus (aav) has many properties of an ideal vector for delivery of therapeutic genes into the myocardium. previous studies in a mouse model of myocardial infarction showed that aav serotype 1 (aav1) is superior to aav serotypes 2-5 to transfer genes into the myocardium by direct injection. since vectors may behave differently in humans and because the human and the pig hearts resemble each other closely, we tested whether aav1 is also superior to aav2 in transferring genes into ...200818044793
adeno-associated virus type 12 (aav12): a novel aav serotype with sialic acid- and heparan sulfate proteoglycan-independent transduction activity.recombinant adeno-associated virus (raav) is a promising vector for gene therapy. recent isolations of novel aav serotypes have led to significant advances by broadening the tropism and increasing the efficiency of gene transfer to the desired target cell. however, a major concern that remains is the strong preexisting immune responses to several vectors. in this paper, we describe the isolation and characterization of aav12, an aav serotype with unique biological and immunological properties. i ...200818045941
application of doxorubicin-induced raav2-p53 gene delivery in combined chemotherapy and gene therapy for hepatocellular carcinoma.p53 gene transfer has been proposed as a potential therapeutic option for treatment of hepatocellular carcinoma (hcc). compared to other commonly used gene transfer vectors such as adenovirus and retrovirus, recombinant adeno-associated virus serotype 2 (raav2) has shown promising results in human clinical trials. significant enhancement in the gene transfer efficiency is needed, however, for hcc applications. in the present study, we applied chemotherapy drug doxorubicin (dox) to induce raav2 t ...200818059187
role of chromatin structure in integration of helper-dependent adenoviral vectors containing the beta-globin locus control region.we constructed helper-dependent, fiber-chimeric adenoviral vectors that efficiently transduce human hematopoietic stem cells. we found that vectors carrying a 23-kb fragment of the beta-globin locus control region (lcr) flanked by adeno-associated virus inverted terminal repeats (ad.lcr) preferentially integrated into the chromosomal beta-globin lcr of human erythroid mo7e cells. we hypothesized that this targeted integration involves beta-globin lcr-specific chromatin structures. chromatin immu ...200818177253
complement is an essential component of the immune response to adeno-associated virus vectors.adeno-associated virus (aav) vectors are associated with relatively mild host immune responses in vivo. although aav induces very weak innate immune responses, neutralizing antibodies against the vector capsid and transgene still occur. to understand further the basis of the antiviral immune response to aav vectors, studies were performed to characterize aav interactions with macrophages. primary mouse macrophages and human thp-1 cells transduced in vitro using an aav serotype 2 (aav2) vector en ...200818199646
production of recombinant adeno-associated viral vectors for in vitro and in vivo use.adeno-associated virus is a nonpathogenic human virus that has been developed into a gene-delivery vector due to its high efficiency of infection in many different cell types and its ability to persist and lead to long-term gene expression. the vector is also a valuable tool in molecular biology experiments. this unit describes efficient methods to generate high-titer, research-grade, adenovirus-free, recombinant single-stranded and self-complementary adeno-associated virus in various serotypes, ...200718265393
chemical rescue of deltaf508-cftr mimics genetic repair in cystic fibrosis bronchial epithelial cells.in a previous study of sodium 4-phenylbutyrate (4-pba)-responsive proteins in cystic fibrosis (cf) ib3-1 bronchial epithelial cells, we identified 85 differentially expressed high abundance proteins from whole cellular lysate (singh, o. v., vij, n., mogayzel, p. j., jr., jozwik, c., pollard, h. b., and zeitlin, p. l. (2006) pharmacoproteomics of 4-phenylbutyrate-treated ib3-1 cystic fibrosis bronchial epithelial cells. j. proteome res. 5, 562-571). in the present work we hypothesize that a subse ...200818285607
antibody-dependent enhancement of adeno-associated virus infection of human monocytic cell lines.in host animals, adeno-associated virus (aav) is detectable mainly in the lymphoid tissue, which appears to be a target in natural infection. we used the human monocytic cell lines thp-1 and u937 to study the effect of mouse anti-aav2 antiserum on infection with an aav2 vector having the luciferase gene (aav2/luc). aav2/luc was found to infect thp-1 and u937 cells much less efficiently than hela cells, as monitored with the induced enzyme activity. pre-incubation of aav2/luc with anti-aav2 antis ...200818295295
inherited diseases of photoreceptors and prospects for gene therapy.the photoreceptor cells of the retina are subject to a wide range of genetic diseases. this review summarizes current knowledge regarding an important group of retinal diseases caused by mutations in photoreceptor-enriched genes. in addition, progress toward treatment of a variety of these diseases in animal models via adeno-associated virus gene therapy is described. although no human trials have yet been initiated to treat diseases caused by mutations in photoreceptor-enriched genes, there is ...200818303969
performance of aav8 vectors expressing human factor ix from a hepatic-selective promoter following intravenous injection into rats.vectors based on adeno-associated virus-8 (aav8) have shown efficiency and efficacy for liver-directed gene therapy protocols following intravascular injection, particularly in relation to haemophilia gene therapy. aav8 has also been proposed for gene therapy targeted at skeletal and cardiac muscle, again via intravascular injection. it is important to assess vector targeting at the level of virion accumulation and transgene expression in multiple species to ascertain potential issues relating t ...200818312698
characterization of human mesothelioma cell lines as tumor models for suicide gene therapy.the median survival time of patients with malignant pleural mesothelioma (mpm) remains poor. therefore, novel therapeutic options are in high demand, and well characterized model systems for in vitro/vivo screening have to be established.200818322411
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