Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
|---|
| leptin resistance exacerbates diet-induced obesity and is associated with diminished maximal leptin signalling capacity in rats. | leptin resistance is generally considered a consequence of obesity. we postulated that leptin resistance is associated with diminished hypothalamic leptin signalling capacity and that leptin resistance is causal to obesity. we assessed maximal leptin-mediated binding of the transcription factor signal transducer and activator of transcription 3 (stat3), and the response to high-fat feeding in lean leptin-resistant rats. | 2005 | 15864530 |
| adeno-associated virus vector-mediated delivery of pigment epithelium-derived factor restricts neuroblastoma angiogenesis and growth. | the purpose of this study was to evaluate the ability of adeno-associated virus (aav) vector-mediated delivery of pigment epithelium-derived factor (pedf) to inhibit neuroblastoma (nb) xenograft growth. pigment epithelium-derived factor was chosen for this study because, in addition to being a potent inhibitor of angiogenesis, it is capable of inducing neuronal differentiation. | 2005 | 15868591 |
| over-expression of the human eaat2 glutamate transporter within neurons of mouse organotypic hippocampal slice cultures leads to increased vulnerability of ca1 pyramidal cells. | excitatory amino acid transporters (eaats) maintain the balance between pathological and physiological conditions by limiting the extracellular concentration of glutamate within the cns and thus preventing excitotoxic injury. the loss of eaat2 has been associated with the development of neurological diseases such as amyotrophic lateral sclerosis. it has therefore been suggested that the over-expression of specific eaats may provide some degree of neuroprotection. however, the inability to isolat ... | 2005 | 15869527 |
| adeno-associated virus: a ubiquitous commensal of mammals. | 2005 | 15871671 | |
| custom adeno-associated virus capsids: the next generation of recombinant vectors with novel tropism. | recombinant gene delivery vehicles based on adeno-associated virus (raav) have emerged as promising vectors for the correction of genetic and acquired human disease states. these vectors possess many characteristics, including low pathogenicity and immunogenicity, and long-term gene expression after a single administered dose, that make them leading candidates for clinical gene therapy applications. yet, the broad tissue tropism of the available aav serotypes remains a disadvantage for the safes ... | 2005 | 15871672 |
| adeno-associated virus pseudotype 5 vector improves gene transfer in arthritic joints. | the potential for gene delivery to joints, using recombinant adeno-associated virus (raav) vectors for the treatment of rheumatoid arthritis (ra), has received much attention. different serotypes have different virion shell proteins and, as a consequence, vary in their tropism for diverse tissues. the aim of this study was to compare the transduction efficiency of different aav serotypes encoding murine secreted alkaline phosphatase (mseap) or escherichia coli beta-galactosidase for intraarticul ... | 2005 | 15871674 |
| gene targeting by adeno-associated virus vectors is cell-cycle dependent. | adeno-associated virus (aav) vectors can be used to introduce site-specific mutations into homologous chromosomal sequences. there are many potential applications of this technique, but the process of aav-mediated gene targeting and factors that influence targeting efficiency are not completely understood. we investigated the dependence of aav-mediated gene targeting on the host cell-cycle status. the frequency of gene targeting by aav vectors was compared in dividing and serum-arrested normal h ... | 2005 | 15871683 |
| development and evaluation of the specificity of a cathepsin d proximal promoter in the eye. | recombinant adeno-associated virus (raav)-mediated gene delivery has emerged as a valuable tool for alternative treatment of ocular diseases. cellular specificity of transgene expression could be influenced by either the viral capsid or the choice of promoter. the use of cellular promoter, cathepsin d (catd) proximal promoter, and its potential for application in raav-based gene therapy are evaluated in this study. | 2005 | 15875365 |
| adeno-associated virus: from defective virus to effective vector. | the initial discovery of adeno-associated virus (aav) mixed with adenovirus particles was not a fortuitous one but rather an expression of aav biology. indeed, as it came to be known, in addition to the unavoidable host cell, aav typically needs a so-called helper virus such as adenovirus to replicate. since the aav life cycle revolves around another unrelated virus it was dubbed a satellite virus. however, the structural simplicity plus the defective and non-pathogenic character of this satelli ... | 2005 | 15877812 |
| therapeutic benefit of th-engineered mesenchymal stem cells for parkinson's disease. | the present study was designed to assess the potential of marrow stromal cells (mscs) to deliver therapeutic genes to the brain and result in biologically significant functional recovery. the tyrosine hydroxylase (th) gene was transfected to mscs with an adeno-associated virus (aav) vector. mscs expressing th gene were transplanted into the striatum of parkinson's disease (pd) rat. the asymmetric rotation of these models after apomorphine administration was detected every week after transplantat ... | 2005 | 15878150 |
| enhanced gene transfer to arthritic joints using adeno-associated virus type 5: implications for intra-articular gene therapy. | gene therapy of the joint has great potential as a new therapeutic approach for the treatment of rheumatoid arthritis (ra). the vector chosen is of crucial importance for clinical success. | 2005 | 15878906 |
| proteasome modulating agents induce raav2-mediated transgene expression in human intestinal epithelial cells. | intestinal gene transfer offers promise as a therapeutic option for treatment of both intestinal and non-intestinal diseases. recombinant adeno-associated virus serotype 2, raav2, based vectors have been utilized to transduce lung epithelial cells in culture and in human subjects. raav2 transduction of intestinal epithelial cells, however, is limited both in culture and in vivo. proteasome-inhibiting agents have recently been shown to enhance raav2-mediated transgene expression in airway epithel ... | 2005 | 15883029 |
| effects of adeno-associated virus dna hairpin structure on recombination. | hairpin dna ends are evolutionarily conserved intermediates in dna recombination. the hairpin structures present on the ends of the adeno-associated virus (aav) genome are substrates for recombination that give rise to persistent circular and concatemeric dna episomes through intramolecular and intermolecular recombination, respectively. we have developed circularization-dependent and orientation-specific self-complementary aav (scaav) vectors as a reporter system to examine recombination events ... | 2005 | 15890919 |
| adeno-associated virus type 2 enhances goose parvovirus replication in embryonated goose eggs. | the autonomous goose parvovirus (gpv) and the human helper-dependent adeno-associated virus type 2 (aav2) share a high degree of homology. to determine if this evolutionary relationship has a biological impact, we studied viral replication in human 293 cells and in embryonated goose eggs coinfected with both viruses. similar experiments were performed with the minute virus of mice (mvm), an autonomous murine parvovirus with less homology to aav2. in human 293 cells, both gpv and mvm augmented aa ... | 2005 | 15892967 |
| effect of polyethylenimine on recombinant adeno-associated virus mediated insulin gene therapy. | recombinant adeno-associated virus (raav) is becoming a promising vector for gene therapy for type i diabetes. the objective of this study was to investigate the effect of incorporation of polyethylenimine (pei) on raav-mediated insulin gene therapy in vitro and in vivo. | 2005 | 15906397 |
| adeno-associated virus vectors in clinical trials. | 2005 | 15916479 | |
| production of recombinant adeno-associated virus vectors. | recombinant adeno-associated virus (raav) is a prototypical gene therapy vector characterized by excellent safety profiles, wide host range, and the ability to transduce differentiated cells. numerous raav-based vectors providing efficient and sustained expression of transgenes in target tissues have been developed for preclinical studies. interest in raav has been driven by advances in production methods originally developed for raav serotype 2 vectors and expanded to include alternative seroty ... | 2005 | 15916480 |
| sustained correction of glycogen storage disease type ii using adeno-associated virus serotype 1 vectors. | glycogen storage disease type ii (gsdii) is caused by a lack of functional lysosomal acid alpha-glucosidase (gaa). affected individuals store glycogen in lysosomes beginning during gestation, ultimately resulting in fatal hypertrophic cardiomyopathy and respiratory failure. we have assessed the utility of recombinant adeno-associated virus (raav) vectors to restore gaa activity in vivo in a mouse model of gsdii (gaa(-/-)). a single systemic administration of a raav serotype 1 (raav1) vector to n ... | 2005 | 15920463 |
| 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 ... | 2005 | 15920464 |
| adeno-associated virus-mediated gene transfer to hair cells and support cells of the murine cochlea. | more than 28 million americans suffer from various forms of hearing loss. the lack of effective treatments for many forms of hearing disorders has prompted interest in the potential application of gene delivery techniques to treat both inherited and pathological hearing disorders. however, to develop a gene therapy strategy that will successfully treat hearing disorders, appropriate vectors that are capable of transducing cochlear hair cells and support cells must be identified. in the present s ... | 2005 | 15922954 |
| correction of glycogen storage disease type ii by an adeno-associated virus vector containing a muscle-specific promoter. | glycogen storage disease type ii (pompe disease) causes death in infancy from cardiorespiratory failure due to acid alpha-glucosidase (gaa; acid maltase) deficiency. an aav2 vector pseudotyped as aav6 (aav2/6 vector) transiently expressed high-level human gaa in gaa-knockout (gaa-ko) mice without reducing glycogen storage; however, in immunodeficient gaa-ko/scid mice the aav2/6 vector expressed high-level gaa and reduced the glycogen content of the injected muscle for 24 weeks. a cd4+/cd8+ lymph ... | 2005 | 15922959 |
| in vivo inhibition of hippocampal ca2+/calmodulin-dependent protein kinase ii by rna interference. | hippocampal alpha-ca2+/calmodulin-dependent protein kinase ii (alpha-camkii) has been implicated in spatial learning, neuronal plasticity, epilepsy, and cerebral ischemia. in the present study, an adeno-associated virus (aav) vector was designed to express green fluorescent protein (gfp) from the cba promoter and a small hairpin rna targeting alpha-camkii (aav-shcam) driven from the u6 promoter. the aav-shcam or control vector was microinfused into the rat hippocampus and behavioral testing cond ... | 2005 | 15922960 |
| widespread and early myocardial gene expression by adeno-associated virus vector type 6 with a beta-actin hybrid promoter. | gene therapy for acute cardiac events such as myocardial infarction requires early gene expression over an entire region of myocardium, which has not been possible using adeno-associated virus (aav) vectors to date. here we demonstrate marked improvement in the distribution and rapidity of gene expression in myocardium using the aav pseudotype 6 (aav6) vector, compared to the standard serotype 2 (aav2) vector. an alkaline phosphatase (ap) reporter construct driven by the chicken beta-actin promo ... | 2005 | 15922969 |
| targeted modification of mammalian genomes. | the stable and site-specific modification of mammalian genomes has a variety of applications in biomedicine and biotechnology. here we outline two alternative approaches that can be employed to achieve this goal: homologous recombination (hr) or site-specific recombination. homologous recombination relies on sequence similarity (or rather identity) of a piece of dna that is introduced into a host cell and the host genome. in most cell types, the frequency of homologous recombination is markedly ... | 2005 | 15925473 |
| gene transfer to dorsal root ganglia by intrathecal injection: effects on regeneration of peripheral nerves. | gene delivery to sensory neurons of the dorsal root ganglion (drg) offers the prospect of developing new clinical interventions against peripheral nerve diseases and disorders. here we show that genes can be transferred to rat drg through lumbar intrathecal injection of delivery vectors into the cerebrospinal fluid. genes could be transferred to drg using polyethylenimine (pei)/dna complexes, lipofectamine 2000/dna complexes, adeno-associated virus vectors, or baculovirus vectors. we also show t ... | 2005 | 15925545 |
| salivary glands as a potential gene transfer target for gene therapeutics of some monogenetic endocrine disorders. | salivary glands (sgs) exhibit several important features which are also common to endocrine glands: self-containment due to a surrounding capsule, highly efficient protein production and the ability to secrete proteins into the bloodstream. we have hypothesized that sgs are potentially useful as gene transfer targets for the correction of inherited monogenetic endocrine disorders. in the present communication, we extend our studies and attempt to test our hypothesis by comparing the efficacy of ... | 2005 | 15930162 |
| gene targeting with viral vectors. | genetic manipulation of cells for scientific and therapeutic goals can be achieved by both gene-addition and gene-targeting methods. gene targeting precisely alters a gene in its natural chromosome location, providing distinct advantages over gene-addition approaches. classic gene-targeting delivery systems (microinjection, electroporation, or calcium phosphate transfection) have led to major scientific advances, but are too inefficient in their current state to be used for some applications, in ... | 2005 | 15932801 |
| 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. | 2005 | 15996030 |
| aav2/5 vector expressing galactocerebrosidase ameliorates cns disease in the murine model of globoid-cell leukodystrophy more efficiently than aav2. | globoid-cell leukodystrophy (gld) is an autosomal recessive lysosomal storage disorder caused by mutations in the galactosylceramidase (galc) gene. infantile gld has a lethal course with severe cerebral demyelination that progresses to death by 2 years of age. in the current study twitcher mice, an authentic murine model of infantile gld, were given intracranial injections of either recombinant adeno-associated virus serotype 2 encoding the murine galc cdna (aav2-galc) or the same genome pseudot ... | 2005 | 15996520 |
| recombinant adeno-associated viral vectors in the nervous system. | recombinant adeno-associated virus 2 (raav2) has been extensively used as a gene delivery vector for the nervous system. it targets primarily neurons in the nervous system and results in sustained long-term expression of transgenes. new raav serotypes have been characterized and demonstrated to have improved transduction efficiencies in various regions of the brain and spinal cord. this review discusses some properties of raav that have been studied in the nervous system such as cell tropism, du ... | 2005 | 16000060 |
| hematopoietic stem cell transduction by recombinant adeno-associated virus vectors: problems and solutions. | recombinant adeno-associated virus 2 (aav) vectors have taken center stage owing to their potentially safer profile compared with the more commonly used retroviral and adenoviral vectors in human gene therapy clinical trials. their remarkable versatility and efficacy in a wide variety of preclinical animal models of human diseases have attracted further attention of a number of investigators. although two particular cell types, muscle and brain, have been shown to be highly transducible by aav v ... | 2005 | 16000061 |
| characterization of a new species of adenovirus in falcons. | in 1996, a disease outbreak occurred at a captive breeding facility in idaho, causing anorexia, dehydration, and diarrhea or sudden death in 72 of 110 northern aplomado falcons (falco femoralis septentrionalis) from 9 to 35 days of age and in 6 of 102 peregrine falcons (falco peregrinus) from 14 to 25 days of age. sixty-two northern aplomado and six peregrine falcons died. epidemiologic analyses indicated a point source epizootic, horizontal transmission, and increased relative risk associated w ... | 2005 | 16000466 |
| evasion of immune responses to introduced human acid alpha-glucosidase by liver-restricted expression in glycogen storage disease type ii. | glycogen storage disease type ii (gsd-ii; pompe disease) is caused by a deficiency of acid alpha-glucosidase (gaa; acid maltase) and manifests as muscle weakness, hypertrophic cardiomyopathy, and respiratory failure. adeno-associated virus vectors containing either a liver-specific promoter (lsp) (aav-lsphgaapa) or a hybrid cb promoter (aav-cbhgaapa) to drive human gaa expression were pseudotyped as aav8 and administered to immunocompetent gaa-knockout mice. secreted hgaa was detectable in plasm ... | 2005 | 16005263 |
| the role of n-methyl-d-aspartate (nmda) receptors in pain and morphine tolerance. | to determine the importance of the n-methyl-d-aspartate (nmda) receptor in pain hypersensitivity following injury, the nmdar1 subunit was selectively deleted in the lumbar spinal cord of adult mice by the localized injection of an adeno-associated virus expressing the cre recombinase into floxed nr1 mice. this procedure resulted in more than an 80% reduction in the expression of both nr1 mrna and protein and a corresponding loss of nmda, but not ampa currents, in the lamina ii neurons in the inj ... | 2005 | 16012411 |
| packaging capacity of adeno-associated virus serotypes: impact of larger genomes on infectivity and postentry steps. | the limited packaging capacity of adeno-associated virus (aav) precludes the design of vectors for the treatment of diseases associated with larger genes. autonomous parvoviruses, such as minute virus of mice and b19, while identical in size (25 nm), are known to package larger genomes of 5.1 and 5.6 kb, respectively, compared to aav genomes of 4.7 kb. one primary difference is the fact that wild-type (wt) aav utilizes three capsid subunits instead of two to form the virion shell. in this study, ... | 2005 | 16014954 |
| pentraxin 3 inhibits fibroblast growth factor 2-dependent activation of smooth muscle cells in vitro and neointima formation in vivo. | the fibroblast growth factor (fgf)/fgf receptor system plays an important role in smooth muscle cell (smc) activation. long-pentraxin 3 (ptx3) is a soluble pattern recognition receptor with non-redundant functions in inflammation and innate immunity. ptx3 is produced by different cell types of the vessel wall, including smcs. ptx3 binds fgf2 and inhibits its angiogenic activity on endothelial cells. we investigated the capacity of ptx3 to affect fgf2-dependent smc activation in vitro and in vivo ... | 2005 | 16020751 |
| aav2-mediated gene delivery to monkey putamen: evaluation of an infusion device and delivery parameters. | in this study, a modified infusion procedure and a novel infusion device designed for use in humans (clinical device b) were evaluated for delivery of recombinant adeno-associated virus (aav2) to brain. the device is composed of 1.2 m of fused silica inserted through a 24.6-cm surgical steel cannula designed to fit a standard leksell clinical stereotaxic frame and micro-infusion syringe pump. aav2 encoding the human aromatic l-amino acid decarboxylase gene (aav-haadc-2) was infused into the puta ... | 2005 | 16022872 |
| evidence for encapsidation of prokaryotic sequences during recombinant adeno-associated virus production and their in vivo persistence after vector delivery. | recombinant adeno-associated virus vectors (raav) have been successfully used for long-term gene expression in animal models and in patients. however, while the therapeutic potential of raav appears promising, safety issues, including contaminants found in vector stocks, must be further evaluated. we previously reported that a cis-acting replication element present within the aav-2 p5 promoter was responsible for the encapsidation of rep-cap sequences observed during raav production. in that stu ... | 2005 | 16023415 |
| long-term evaluation of aav-mediated sflt-1 gene therapy for ocular neovascularization in mice and monkeys. | vascular endothelial growth factor (vegf) is one of the major mediators of retinal ischemia-associated neovascularization. we have shown here that adeno-associated virus (aav)-mediated expression of sflt-1, a soluble form of the flt-1 vegf receptor, was maintained for up to 8 and 17 months postinjection in mice and in monkeys, respectively. the expression of sflt-1 was associated with the long-term (8 months) regression of neovascular vessels in 85% of trvegf029 eyes. in addition, it resulted in ... | 2005 | 16023893 |
| raav-mediated stable expression of heme oxygenase-1 in stellate cells: a new approach to attenuate liver fibrosis in rats. | liver fibrosis is the consequence of activation of hepatic stellate cells mediated by persistent or recurrent liver injury, where oxidative stress or inflammatory response resulting from immune cells and cytokines are involved. targeting of hepatic stellate cells could be an important strategy for the therapy of liver fibrosis. in this study, we showed a tropism of recombinant adeno-associated virus (raav, serotype 2) with high efficiency in transduction of a homeostatic gene, heme oxygenase-1 ( ... | 2005 | 16025519 |
| 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. | 2005 | 16038629 |
| aav serotype-dependent apolipoprotein a-i milano gene expression. | recent evidence from a double-blind, randomized study showed that treatment with apolipoprotein a-i milano (apoa-i milano) in a complex with phospholipids produced significant regression of the coronary atheroma burden in patients with acute coronary syndromes. we previously showed similar regression of atherosclerosis in an animal model. here, we examined a viral vector-based gene delivery system as a basis for apoa-i milano gene therapy. comparing levels of expression using combinations of the ... | 2005 | 16039279 |
| biological effects of raav-caalk2 coating on structural allograft healing. | structural bone allografts often fracture due to their lack of osteogenic and remodeling potential. to overcome these limitations, we utilized allografts coated with recombinant adeno-associated virus (raav) that mediate in vivo gene transfer. using beta-galactosidase as a reporter gene, we show that 4-mm murine femoral allografts coated with raav-lacz are capable of transducing adjacent inflammatory cells and osteoblasts in the fracture callus following transplantation. while this lacz vector h ... | 2005 | 16043092 |
| 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 ... | 2005 | 16043094 |
| no evidence for tumorigenesis of aav vectors in a large-scale study in mice. | six hundred ninety-five mice received adeno-associated virus (aav) vectors, mostly via portal vein injection. at necropsy, the livers were inspected for tumors, and tissue sections were prepared for histology. we observed only one tumor, a lipoma, resulting in a tumor frequency of 0.14%. this tumor contained fewer vector genomes per total dna than the surrounding liver tissue, as shown by quantitative pcr. in another mouse we found a macroscopically visible nodule containing lymphocytes. immunoh ... | 2005 | 16043099 |
| cd151 promotes neovascularization and improves blood perfusion in a rat hind-limb ischemia model. | to evaluate the efficiency of recombinant adeno-associated virus (raav)-mediated cd151 gene delivery in promoting neovascularization and improving blood perfusion in the skeletal muscle of the rat hind-limb ischemia model. | 2005 | 16048379 |
| aav2-mediated cln2 gene transfer to rodent and non-human primate brain results in long-term tpp-i expression compatible with therapy for lincl. | late infantile neuronal ceroid lipofuscinosis (lincl) is a fatal, autosomal recessive disease resulting from mutations in the cln2 gene with consequent deficiency in its product tripeptidyl peptidase i (tpp-i). in the central nervous system (cns), the deficiency of tpp-i results in the accumulation of proteins in lysosomes leading to a loss of neurons causing progressive neurological decline, and death by ages 10-12 years. to establish the feasibility of treating the cns manifestations of lincl ... | 2005 | 16052206 |
| adeno-associated virus vector-mediated gene delivery to the vasculature and kidney. | relatively successful elsewhere, gene delivery aimed at the vasculature and kidney has made very little progress. in the kidney, the hurdles are related to the unique structure-function relationships of this organ and in the blood vessels to a variety of, mostly endothelial, factors making the delivery of transgenes very difficult. among gene-therapeutic approaches, most viral gene delivery systems utilized to date have shown significant practical and safety-related limitations due to the level ... | 2005 | 15940344 |
| targeting site-specific chromosome integration. | the concept of gene therapy was introduced with great promise and high expectations. however, what appeared simple in theory has not translated into practice. despite some success in clinical trials, the research community is still facing an old problem: namely, the need for a vector that can deliver a gene to target cells without adverse events while maintaining a long-term therapeutic effect. some of these challenges are being addressed by the development of hybrid vectors which meld two diffe ... | 2005 | 15940345 |
| adeno-associated virus (aav)-7 and -8 poorly transduce vascular endothelial cells and are sensitive to proteasomal degradation. | transduction of the vascular endothelium by adeno-associated virus (aav) vectors would have broad appeal for gene therapy. however, levels of transduction by aav serotype-2 are low, an observation linked to deficiencies in endothelial cell binding, sequestration of virions in the extracellular matrix and/or virion degradation by the proteasome. strategies to improve transduction of endothelial cells include aav-2 capsid targeting using small peptides isolated by phage display or the use of alter ... | 2005 | 15944729 |
| adeno-associated virus type 4 (aav4) targets ependyma and astrocytes in the subventricular zone and rms. | the subventricular zone (svz) is one of the neurogenic niches in the adult mammalian brain. the svz is of interest for studies on neurogenesis and stem cell therapy. here, we report specific transduction of ependyma and/or astrocytes by recombinant adeno-associated virus type 4 (aav4) viral vectors. aav4 vectors encoding beta-galactosidase or egfp were injected into the lateral ventricles of neonatal and adult c57bl/6 mouse brains. in addition, svz injections were conducted on adult mice. aav4 v ... | 2005 | 15944733 |
| a cmv-actin-globin hybrid promoter improves adeno-associated viral vector gene expression in the arterial wall in vivo. | adeno-associated virus (aav) vectors are attractive tools for direct intralumenal arterial gene transfer in interventional cardiology or cardiovascular surgery, but clinical application has been constrained by poor gene expression in this setting. | 2005 | 15945122 |
| adeno-associated virus serotypes 1 to 5 mediated tumor cell directed gene transfer and improvement of transduction efficiency. | gene therapy is an attractive new approach for the treatment of cancer. therefore, the development of efficient vector systems is of crucial importance in this field. different adeno-associated virus (aav) serotypes have been characterized so far, which show considerable differences in tissue tropism. consequently, we aimed to characterize the most efficient serotype for this application. | 2005 | 15945124 |
| an optimized protocol for detection of e. coli beta-galactosidase in lung tissue following gene transfer. | staining by 5-bromo-4-chloro-3-indolyl-beta-d: -galactopyranoside (x-gal) typically detects activity of e. coli beta-galactosidase (beta-gal) in transduced tissues that express the lacz reporter gene. in lung tissue from mice that received beta-galactosidase-expressing adeno-associated virus (aav) vectors via intranasal inhalation, we observed only a low frequency of positive cells after x-gal staining in contrast to other reporter genes, such as alkaline phosphatase or green fluorescent protein ... | 2005 | 15947941 |
| inhibitory effect of adeno-associated virus-mediated gene transfer of human endostatin on hepatocellular carcinoma. | to investigate the effect of adeno-associated virus-mediated gene transfer of human endostatin on the growth of hepatocellular carcinoma (hcc). | 2005 | 15948234 |
| [expression of enhanced green fluorescent protein in rat brain transduced by recombinant adeno-associated viruses type 1 and type 2]. | to explore the expression of enhanced green fluorescent protein (egfp) transduced into the brain via recombinant adeno-associated virus (raav) type 1 and raav type 2 vectors so as to select the better raav serotype and feasible gene transfer route to central nervous system (cns). | 2005 | 15949335 |
| perigestational suppression of weight gain with central leptin gene therapy results in lower weight f1 generation. | the efficacy of central leptin therapy on weight homeostasis through various phases of reproduction, pregnancy outcome and postnatal, prepubertal and pubertal growth of offspring was assessed. enhanced leptin transgene expression after a single intracerebroventricular injection of recombinant adeno-associated virus vector encoding the leptin gene (raav-lep) decreased calorie intake and weight in adult nulliparous female rats. raav-lep treated rats conceived normally, displayed unremarkable pregn ... | 2005 | 15949636 |
| [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. | 2005 | 15958300 |
| stabilized hif-1alpha is superior to vegf for angiogenesis in skeletal muscle via adeno-associated virus gene transfer. | therapeutic angiogenesis provides a potential alternative for the treatment of cardiovascular ischemic diseases. vascular endothelial growth factor (vegf) is an important component of the angiogenic response to ischemia. here we used adeno-associated virus (aav) gene delivery to skeletal muscle to examine the effects of vegf vs. a stabilized form of hypoxia-inducible factor-1alpha (hif-1alpha). the recombinant aavs were injected into mouse tibialis anterior muscle, and their effects were analyze ... | 2005 | 15958522 |
| adeno-associated virus-mediated gene transfer for lung diseases. | 2005 | 15960596 | |
| 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 ... | 2005 | 15960597 |
| adeno-associated virus 2-mediated intratumoral prostate cancer gene therapy: long-term maspin expression efficiently suppresses tumor growth. | maspin is a member of the serine protease inhibitors and the maspin gene, a tumor suppressor gene, is down-regulated in a large fraction of prostate cancers. we evaluated the use of adeno-associated virus (aav, serotype 2) vector encoding maspin as a means for in vivo gene therapy for human prostate cancer. tunel assay of subcutaneously formed lncap or du145 tumors in nude mice showed that intratumoral aav-mediated maspin expression significantly upregulated the number of apoptotic cells compare ... | 2005 | 15960601 |
| adeno-associated virus vectors: potential applications for cancer gene therapy. | augmenting cancer treatment by protein and gene delivery continues to gain momentum based on success in animal models. the primary hurdle of fully exploiting the arsenal of molecular targets and therapeutic transgenes continues to be efficient delivery. vectors based on adeno-associated virus (aav) are of particular interest as they are capable of inducing transgene expression in a broad range of tissues for a relatively long time without stimulation of a cell-mediated immune response. perhaps t ... | 2005 | 15962012 |
| ifn-alpha gene therapy for woodchuck hepatitis with adeno-associated virus: differences in duration of gene expression and antiviral activity using intraportal or intramuscular routes. | gene delivery of ifn-alpha to the liver may represent an interesting strategy to maximize its antiviral efficacy and reduce side effects. we used a recombinant adeno-associated virus (aav) encoding woodchuck ifn-alpha (aav-ifn) to treat animals with chronic woodchuck hepatitis virus infection. the vector was given by intraportal or intramuscular route. long-term transgene expression was detected after intraportal administration of an aav encoding luciferase. in contrast, in the majority of the a ... | 2005 | 15963922 |
| helper functions required for wild type and recombinant adeno-associated virus growth. | the human parvovirus adeno-associated virus (aav-2) has been classified as a dependovirus because it requires the presence of a helper virus to achieve a productive replication cycle. several viruses such as adenovirus (ad), herpes simplex virus (hsv), vaccinia virus, and human papillomaviruses (hpv) can provide the helper activities required for aav growth. the studies on the helper activities provided by adenovirus have provided useful information not only to understand the aav-2 biology but a ... | 2005 | 15975004 |
| mechanisms of adeno-associated virus genome encapsidation. | the defective parvovirus, adeno-associated virus (aav), is under close scrutiny as a human gene therapy vector. aav's non-pathogenic character, reliance on helper virus co-infection for replication and wide tissue tropism, make it an appealing vector system. the virus' simplicity and ability to generate high titer vector preparations have contributed to its wide spread use in the gene therapy community. the single stranded aav dna genome is encased in a 20-25 nm diameter, icosahedral protein cap ... | 2005 | 15975005 |
| aav hybrid serotypes: improved vectors for gene delivery. | in recent years, significant efforts have been made on studying and engineering adeno-associated virus (aav) capsid, in order to increase efficiency in targeting specific cell types that are non-permissive to wild type (wt) viruses and to improve efficacy in infecting only the cell type of interest. with our previous knowledge of the viral properties of the naturally occurring serotypes and the elucidation of their capsid structures, we can now generate capsid mutants, or hybrid serotypes, by va ... | 2005 | 15975007 |
| adeno-associated viral vectors for clinical gene transfer studies. | recombinant adeno-associated viral (raav) vectors can mediate the safe and long-term correction of genetic diseases in animal models following a single administration. these pre-clinical studies are the basis of human trials that have shown raav vector persistence and safety in humans following delivery to lung, sinus, skeletal muscle, brain and liver. transient disease correction has also been demonstrated in humans treated for hemophilia b and cystic fibrosis using aav2 vectors. the physiochem ... | 2005 | 15975008 |
| immune responses to adeno-associated virus vectors. | one of the biggest challenges in optimizing viral vectors for gene therapy relates to the immune response of the host. adeno-associated virus (aav) vectors are associated with low immunogenicity and toxicity, resulting in vector persistence and long-term transgene expression. the inability of aav vectors to efficiently transduce or activate antigen presenting cells (apcs) may account for their decreased immunogenicity. aav mediated gene therapy however, leads to the development of antibodies aga ... | 2005 | 15975009 |
| adeno-associated virus (aav) vectors in the cns. | adeno-associated virus (aav) vectors exhibit a number of properties that have made this vector system an excellent choice for both cns gene therapy and basic neurobiological investigations. in vivo, the preponderance of aav vector transduction occurs in neurons where it is possible to obtain long-term, stable gene expression with very little accompanying toxicity. promoter selection, however, significantly influences the pattern and longevity of neuronal transduction distinct from the tropism in ... | 2005 | 15975010 |
| activation of the extracellular signal-regulated kinase 1/2 pathway by aav gene transfer protects retinal ganglion cells in glaucoma. | glaucoma is the second leading cause of blindness in the world. loss of vision in glaucomatous optic neuropathy is caused by the selective degeneration of retinal ganglion cells (rgcs). ocular hypertension is a major risk factor in glaucoma, but visual field defects continue to progress in some patients despite the use of drugs that lower intraocular pressure. at present, there are no effective neuroprotective strategies for the treatment of this disease. the extracellular signal-regulated kinas ... | 2005 | 15975850 |
| gene therapy for colon cancer by adeno-associated viral vector-mediated transfer of survivin cys84ala mutant. | reactivation of survivin expression is involved in carcinogenesis and angiogenesis in colon cancer. previous in vitro studies showed that mutation of the cysteine residue at position 84 (cys84ala) of survivin generates a dominant-negative mutant that triggers mitotic catastrophe and apoptosis. we investigated the therapeutic effect of the adeno-associated virus (aav)-mediated survivin mutant (cys84ala) on colon cancer. | 2005 | 15685548 |
| aav-mediated hippocampal expression of short and long homer 1 proteins differentially affect cognition and seizure activity in adult rats. | homer proteins mediate molecular rearrangements leading to changes in spine morphology. this points to a role of homer in learning and memory. homer 1c features both the ligand binding domain and a coiled-coiled domain for self-multimerization. homer 1a lacks the coiled-coiled domain. here, we report a new isoform which we termed 1g, lacking the homer ligand binding domain. we dissected the functional roles of the individual homer 1 domains, encoded by homer 1a, 1c, and 1g, in vivo. recombinant ... | 2005 | 15691715 |
| femoral intra-arterial injection: a tool to deliver and assess recombinant aav constructs in rodents whole hind limb. | with the aim of simplifying recombinant-adeno-associated virus (raav) delivery in muscle, a new femoral intra-arterial technique was designed and tested in rodents (rats and mice). two serotypes, several promoters and transgenes (reporter or therapeutic) were tested using this administration route. the new route is both easy to perform and efficient. its usefulness as a tool to assess gene delivery constructs in the muscle was established in the context of recombinant aav serotypes 1 and 2, and ... | 2005 | 15693034 |
| a shortened adeno-associated virus expression cassette for cftr gene transfer to cystic fibrosis airway epithelia. | adeno-associated viruses (aavs) such as aav5 that transduce airway epithelia from the apical surface are attractive vectors for gene transfer in cystic fibrosis (cf). however, their utility in cf has been limited because packaging of the insert becomes inefficient when its length exceeds approximately 4,900-5,000 bp. to partially circumvent this size constraint, we previously developed a cf transmembrane conductance regulator (cftr) transgene that deleted a portion of the r domain (cftrdeltar). ... | 2005 | 15703296 |
| transduction of the choroid plexus and ependyma in neonatal mouse brain by vesicular stomatitis virus glycoprotein-pseudotyped lentivirus and adeno-associated virus type 5 vectors. | evaluation of gene transfer into the developing mouse brain has shown that when adeno-associated virus serotype 1 (aav1) or aav2 vectors are injected into the cerebral lateral ventricles at birth, widespread parenchymal transduction occurs. lentiviral vectors have not been tested by this route. in this study, we found that injection of lentiviral vectors pseudotyped with vesicular stomatitis virus glycoprotein (vsv-g) resulted in targeted transduction of the ependymal cells lining the ventricula ... | 2005 | 15703488 |
| impact of humoral immune response on distribution and efficacy of recombinant adeno-associated virus-derived acid alpha-glucosidase in a model of glycogen storage disease type ii. | glycogen storage disease type ii (gsdii) is a lysosomal storage disease caused by a deficiency in acid alpha-glucosidase (gaa), and leads to cardiorespiratory failure by the age of 2 years. in this study, we investigate the impact of anti-gaa antibody formation on cross-correction of the heart, diaphragm, and hind-limb muscles from liver-directed delivery of recombinant adeno-associated virus (raav)5- and raav8-gaa vectors. gaa(-/-) mice receiving 1 x 10(12) vector genomes of raav5- or raav8-dhb ... | 2005 | 15703490 |
| transfer of the full-length dystrophin-coding sequence into muscle cells by a dual high-capacity hybrid viral vector with site-specific integration ability. | duchenne muscular dystrophy (dmd) is caused by mutations in the dmd gene, making it a potential target for gene therapy. there is, however, a scarcity of vectors that can accommodate the 14-kb dmd cdna and permanently genetically correct muscle tissue in vivo or proliferating myogenic progenitors in vitro for use in autologous transplantation. here, a dual high-capacity adenovirus-adeno-associated virus (hcad/aav) vector with two full-length human dystrophin-coding sequences flanked by aav integ ... | 2005 | 15709034 |
| recombinant adeno-associated virus 2-mediated antiangiogenic prevention in a mouse model of intraperitoneal ovarian cancer. | in the present study, we sought to determine the potential of sustained transgene expression by a single i.m. administration of recombinant adeno-associated virus 2 (raav) encoding angiostatin and endostatin in inhibiting i.p. ovarian cancer growth and dissemination in a preclinical mouse model. | 2005 | 15709207 |
| gene therapy of metachromatic leukodystrophy. | metachromatic leukodystrophy (mld) is a lysosomal storage disease that is caused by a deficiency of arylsulfatase a (asa). the deficiency results in the intralysosomal accumulation of the acidic sphingolipid 3-o-sulfogalactosyl-ceramide (sulfatide). patients suffer from progressive demyelination and die from multiple neurological deficits. curative treatment is not available. asa bears mannose 6-phosphate residues which function as recognition markers in endosome/lysosome-specific targeting path ... | 2005 | 15709909 |
| recombinant adeno-associated virus (raav) expressing tfpi-2 inhibits invasion, angiogenesis and tumor growth in a human glioblastoma cell line. | recombinant adeno-associated viruses (raav) have become the vector of choice for many gene therapy protocols. raavs have a number of attractive features including long-term transgene expression and the ability to transduce both dividing and non-dividing cells. we have shown previously the anti-cancer role of tissue factor pathway inhibitor-2 (tfpi-2), a matrix-associated serine protease inhibitor, in human glioblastomas. as a result of our present study, in which 0.8-kb fragment of human tfpi-2 ... | 2005 | 15723303 |
| stable secondary structure near the nicking site for adeno-associated virus type 2 rep proteins on human chromosome 19. | adeno-associated virus serotype 2 (aav-2) can preferentially integrate its dna into a 4-kb region of human chromosome 19, designated aavs1. the nicking activity of aav-2's rep68 or rep78 proteins is essential for preferential integration. these proteins nick at the viral origin of dna replication and at a similar site within aavs1. the current nicking model suggests that the strand containing the nicking site is separated from its complementary strand prior to nicking. in aav serotypes 1 through ... | 2005 | 15731249 |
| large-scale molecular characterization of adeno-associated virus vector integration in mouse liver. | recombinant adeno-associated virus (raav) vector holds promise for gene therapy. despite a low frequency of chromosomal integration of vector genomes, recent studies have raised concerns about the risk of raav integration because integration occurs preferentially in genes and accompanies chromosomal deletions, which may lead to loss-of-function insertional mutagenesis. here, by analyzing 347 raav integrations in mice, we elucidate novel features of raav integration: the presence of hot spots for ... | 2005 | 15731255 |
| effective gene therapy for an inherited cns disease in a large animal model. | genetic diseases affecting the brain typically have widespread lesions that require global correction. lysosomal storage diseases are good candidates for central nervous system gene therapy, because active enzyme from genetically corrected cells can be secreted and taken up by surrounding diseased cells, and only small amounts of enzyme (<5% of normal) are required to reverse storage lesions. injection of gene transfer vectors into multiple sites in the mouse brain has been shown to mediate wide ... | 2005 | 15732095 |
| adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart. | systemic gene delivery into muscle has been a major challenge for muscular dystrophy gene therapy, with capillary blood vessels posing the principle barrier and limiting vector dissemination. previous efforts to deliver genes into multiple muscles have relied on isolated vessel perfusion or pharmacological interventions to enforce broad vector distribution. we compared the efficiency of multiple adeno-associated virus (aav) vectors after a single injection via intraperitoneal or intravenous rout ... | 2005 | 15735640 |
| valproic acid enhances gene expression from viral gene transfer vectors. | viral vectors represent an efficient delivery method for in vitro and in vivo gene transfer, and their utility may be further enhanced through the use of pharmacologic agents that increase gene expression. here, we demonstrate that valproic acid (vpa), a drug which is widely used for the treatment of epilepsy and mood disorders, enhances and prolongs expression of exogenous genes in cells transduced with various gene transfer agents, including adenovirus, adeno-associated virus and herpesvirus v ... | 2005 | 15737413 |
| the adeno associated viral vector as a strategy for intradiscal gene transfer in immune competent and pre-exposed rabbits. | experimental animal study. | 2005 | 15738780 |
| overexpression of soluble trail induces apoptosis in human lung adenocarcinoma and inhibits growth of tumor xenografts in nude mice. | recombinant adeno-associated virus 2/5 (raav2/5), a hybrid raav-2 with aav-5 capsid, seems to be a very efficient delivery vector for the transduction of the lung adenocarcinoma cell line a549. infection of the a549 cell line with a raav2/5 vector encoding the extracellular domain of tumor necrosis factor-related apoptosis-inducing ligand (trail, amino acids 114-281) resulted in secretion of soluble trail (strail) and induction of apoptosis in these cells. raav2/5-strail mediated delivery and st ... | 2005 | 15753363 |
| a dna recombination-based approach to eliminate papillomavirus infection. | at present, no treatments exist that effectively target and eliminate papillomaviruses (pvs) from infected cells or prevent its replication. we are employing a strategy to prevent virus replication in pv-infected cells through the conditional expression of the herpes simplex virus type 1 thymidine kinase (tk) gene. expression of tk in this system is expected to be triggered by a homologous recombination event between the endogenous pv genome and a nonexpressing tk gene cassette. recombination be ... | 2005 | 15756291 |
| stable inhibition of hepatitis b virus proteins by small interfering rna expressed from viral vectors. | there has been much research into the use of rna interference (rnai) for the treatment of human diseases. many viruses, including hepatitis b virus (hbv), are susceptible to inhibition by this mechanism. however, for rnai to be effective therapeutically, a suitable delivery system is required. | 2005 | 15756649 |
| improved neuronal transgene expression from an aav-2 vector with a hybrid cmv enhancer/pdgf-beta promoter. | adeno-associated virus type 2 (aav-2) vectors are highly promising tools for gene therapy of neurological disorders. after accommodating a cellular promoter, aav-2 vectors are able to drive sustained expression of transgene in the brain. this study aimed to develop aav-2 vectors that also facilitate a high level of neuronal expression by enhancing the strength of a neuron-specific promoter, the human platelet-derived growth factor beta-chain (pdgf) promoter. | 2005 | 15756650 |
| [effects of cd151 on migration of human tongue squamous carcinoma cell line tca8113]. | over-expression of cd151 gene in tumor tissues may be associated with metastasis and poor prognosis of cancer, but the mechanism is unknown. this study was designed to determine the effects of cd151 gene on migration of human tongue squamous carcinoma cell line tca8113. | 2005 | 15757524 |
| [construction of an adeno-associated virus vector expressing ctla-4ig and its expression in the transplanted liver allografts]. | to construct a recombinant adeno-associated virus vector psnav expressing ctla-4ig and to demonstrate its expression in transplanted liver allografts and to see if a long term inhibitive effect of ctla-4ig could be obtained though its use. | 2005 | 15760550 |
| [binding and inhibition of adeno-associated virus rep78 protein with hepatitis b virus c promoter]. | adeno-associated virus (aav) rep78 is known for its inhibitory effects on replication of several viruses and oncogenes transformations. the study was to investigate the effect of rep78 on hepatitis b virus c (hbv-c) gene and the mechanism of it. | 2005 | 15760551 |
| long-term inducible gene expression in the eye via adeno-associated virus gene transfer in nonhuman primates. | adeno-associated viral gene therapy has shown promise for the treatment of inherited and degenerative diseases in a variety of animal models. some of the most dramatic results have been obtained in the field of ocular gene therapy, where efficacy has been tremendous in inherited and acquired retinal disorders. for the promise of this approach to be realized it will be necessary to create vectors capable of pharmacologic or physiologic regulation of the transgene. we describe in this paper a dime ... | 2005 | 15761258 |
| efficient transduction of vascular endothelial cells with recombinant adeno-associated virus serotype 1 and 5 vectors. | recombinant adeno-associated virus (raav) has become an attractive tool for gene therapy because of its ability to transduce both dividing and nondividing cells, elicit a limited immune response, and the capacity for imparting long-term transgene expression. previous studies have utilized raav serotype 2 predominantly and found that transduction of vascular cells is relatively inefficient. the purpose of the present study was to evaluate the transduction efficiency of raav serotypes 1 through 5 ... | 2005 | 15761263 |
| delivery of mdr1 small interfering rna by self-complementary recombinant adeno-associated virus vector. | small interfering rnas (sirnas) are potentially powerful tools for therapeutic gene regulation. dna cassettes encoding rna polymerase iii promoter-driven hairpin sirnas allow long-term expression of sirna in targeted cells. a variety of viral vectors have been used to deliver such cassettes to cells. here we report on the development and use of a self-complementary recombinant adeno-associated virus (scaav) vector for sirna delivery into mammalian cells. we demonstrate that this modified vector ... | 2005 | 15771955 |
| proteasome inhibition enhances aav-mediated transgene expression in human synoviocytes in vitro and in vivo. | to explore the potential applicability of recombinant adeno-associated virus (raav) vectors in the treatment of rheumatoid arthritis (ra), primary human fibroblast-like synoviocytes (fls) derived from patients with ra were infected with raav encoding mouse il-10 under the control of the cmv promoter. addition of the proteasome inhibitor carbobenzoxy-l-leucyl-l-leucyl-l-leucinal (zlll) to the cultures dramatically enhanced expression of the il-10 transgene, in a dose-dependent manner. the increas ... | 2005 | 15771962 |
| [recombinant adeno-associated virus 2-mediated green fluorescent protein expression in bone marrow mesenchymal stem cells derived from acute myelogenous leukemia patients]. | to explore the possibility of using autologous bone marrow mesenchymal stem cells (bmsc) as a vehicle to deliver recombinant adeno-associated virus 2-mediated enhanced green fluorescent protein (raav-2-egfp) in vitro, therefore to find an alternative solution for gene therapy of hematological malignancy. | 2005 | 15771993 |
| [gene therapy for alzheimer' s disease]. | one of the keys to successful gene therapy is the selection of the appropriate therapeutic gene and its molecular vehicle. a recombinant adeno-associated virus (raav) vector offers the advantage of the ability to infect non-dividing cells, affording a non-pathogenic, long-term transgene expression without a substantial inflammatory response. in alzheimer's disease (ad), accumulation of amyloid-beta peptide (abeta) in the brain is a triggering event leading to the long-term pathological cascade. ... | 2005 | 15773336 |