Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
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| 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 |
| antitumor efficacy of aav-mediated systemic delivery of interferon-beta. | type i interferons (alpha/beta) have significant antitumor activity although their short half-life and systemic side effects have limited their clinical utility. an alternative dosing schedule of continuous, low-level delivery, as is achieved by gene therapy, rather than intermittent, high concentration pulsed-dosing, might avoid the toxicity of interferon while maintaining its antitumor efficacy. we have tested a gene therapy approach in murine tumor models to treat malignancies that have shown ... | 2006 | 16052229 |
| the hypothalamic arcuate nucleus: a key site for mediating leptin's effects on glucose homeostasis and locomotor activity. | leptin is required for normal energy and glucose homeostasis. the hypothalamic arcuate nucleus (arh) has been proposed as an important site of leptin action. to assess the physiological significance of leptin signaling in the arh, we used mice homozygous for a flpe-reactivatable, leptin receptor null allele (lepr(neo/neo) mice). similar to lepr(db/db) mice, these mice are obese, hyperglycemic, hyperinsulinemic, infertile, and hypoactive. to selectively restore leptin signaling in the arh, we gen ... | 2005 | 16054045 |
| gene therapy in epilepsy. | the generation of viral vectors, such as adeno-associated virus (aav) and lentivirus, which are capable of stable transduction of neurons, offers an attractive strategy for introducing novel genes into the brain, resulting in a long-lasting production of specific proteins. an alternative approach to achieving transgene expression in brain is to graft cells that are genetically engineered to produce neuroactive substances. neuroactive peptides, adenosine, and gamma-aminobutyric acid, are agents t ... | 2004 | 16059458 |
| inhibition of lymphogenous metastasis using adeno-associated virus-mediated gene transfer of a soluble vegfr-3 decoy receptor. | the presence of metastases in regional lymph nodes is a strong indicator of poor patient survival in many types of cancer. it has recently been shown that the lymphangiogenic growth factor, vascular endothelial growth factor-c (vegf-c), and its receptor, vegf receptor-3 (vegfr3), may play a pivotal role in the promotion of metastasis to regional lymph nodes. in this study, human prostate and melanoma tumor models that preferentially metastasize to the lymph nodes following s.c. tumor cell implan ... | 2005 | 16061674 |
| correlation between dna transfer and cystic fibrosis airway epithelial cell correction after recombinant adeno-associated virus serotype 2 gene therapy. | recombinant adeno-associated virus serotype 2 (raav2)-based human gene therapy for cystic fibrosis has progressed through a series of preclinical studies and phase i and ii clinical trials. this agent has shown an encouraging safety profile, consistent levels of dna transfer, and positive evidence of short-term clinical improvement in lung function in a prospective, placebo-controlled phase ii trial of aerosol administration. nonetheless, it has been difficult to assess the relationship between ... | 2005 | 16076250 |
| 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 ... | 2005 | 16076253 |
| [construction of adeno-associated virus vector containing human papilloma virus 16 e7 gene and its expression in eukaryotic cells]. | to construct recombinant adeno-associated virus vector containing human papilloma virus (hpv) 16e7 gene and identify its effectiveness of expression in eukaryotic cell. | 2005 | 16080877 |
| efficient hepatic delivery and expression from a recombinant adeno-associated virus 8 pseudotyped alpha1-antitrypsin vector. | alpha1-antitrypsin (aat) deficiency is a single-gene disorder in which a mutation in the aat (approved symbol serpina1) gene (pi*z) leads to misfolding of the protein, loss of the protective antiprotease effect of aat for the lungs, and a toxic effect on hepatocytes. optimal therapy for aat deficiency will require a high percentage of hepatocyte transduction to be effective for liver and lung disease. recently, raav genomes pseudotyped with capsids from serotypes 7 and 8 showed efficient hepatic ... | 2005 | 16085464 |
| [gene therapy in liver diseases using adeno-associated virus as a vector]. | 2005 | 16093007 | |
| adeno-associated virus vector-mediated anti-angiogenic gene therapy for collagen-induced arthritis in mice. | the goal of this study was to determine the utility of adeno-associated virus (aav) vectors for anti-angiogenic gene therapy in a mouse model of collagen-induced arthritis (cia). | 2005 | 16095112 |
| 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 ... | 2005 | 16099413 |
| persistent liver expression of murine apoa-l using vectors based on adeno-associated viral vectors serotypes 5 and 1. | plasma levels of high-density lipoprotein-cholesterol (hdl-c) and apolipoprotein a-l (apoa-l) are inversely related to risk for coronary heart disease. overexpression of apoa-l inhibits atherosclerosis in animal models. a method of stably expressing apoa-l using somatic gene transfer would be of interest. pseudotyped adeno-associated virus (aav) vectors comprised of inverted terminal repeats from aav serotype 2 have been used for liver-directed gene transfers. we hypothesized that liver-directed ... | 2006 | 16099465 |
| a combination of mutations enhances the neurotropism of aav-2. | there is strong interest in developing practical strategies for gene delivery to the central nervous system (cns). direct delivery into the brain or spinal cord is highly invasive as well as inefficient or hazardous using most current vector systems. our objective was to generate innocuous gene vehicles that would be effectively taken up by axons and then home to the neuron cell bodies. vectors derived from adeno-associated virus (aav), a harmless human parvovirus, offer strong starting candidat ... | 2005 | 16102794 |
| a capsid-modified helper-dependent adenovirus vector containing the beta-globin locus control region displays a nonrandom integration pattern and allows stable, erythroid-specific gene expression. | gene therapy for hemoglobinopathies requires efficient gene transfer into hematopoietic stem cells and high-level erythroid-specific gene expression. toward this goal, we constructed a helper-dependent adenovirus vector carrying the beta-globin locus control region (lcr) to drive green fluorescent protein (gfp) expression, whereby the lcr-gfp cassette is flanked by adeno-associated virus (aav) inverted terminal repeats (ad.lcr-beta-gfp). this vector possesses the adenovirus type 35 fiber knob th ... | 2005 | 16103151 |
| the expression strategy of goose parvovirus exhibits features of both the dependovirus and parvovirus genera. | the rna transcription profile of the goose parvovirus (gpv) was determined, and it is a surprising hybrid of features of the parvovirus and dependovirus genera of the parvovirinae subfamily of the parvoviridae. similar to the dependovirus adeno-associated virus type 5, rnas transcribed from the gpv upstream p9 promoter, which encode the viral nonstructural proteins, were polyadenylated at a high efficiency at a polyadenylation site [(pa)p] located within an intron in the center of the genome. ef ... | 2005 | 16103154 |
| the cellular tata binding protein is required for rep-dependent replication of a minimal adeno-associated virus type 2 p5 element. | the p5 promoter region of adeno-associated virus type 2 (aav-2) is a multifunctional element involved in rep gene expression, rep-dependent replication, and site-specific integration. we initially characterized a 350-bp p5 region by its ability to behave like a cis-acting replication element in the presence of rep proteins and adenoviral factors. the objective of this study was to define the minimal elements within the p5 region required for rep-dependent replication. assays performed in transfe ... | 2005 | 16103159 |
| large-scale analysis of adeno-associated virus vector integration sites in normal human cells. | the integration sites of viral vectors used in human gene therapy can have important consequences for safety and efficacy. however, an extensive evaluation of adeno-associated virus (aav) vector integration sites has not been completed, despite the ongoing use of aav vectors in clinical trials. here we have used a shuttle vector system to isolate and analyze 977 unique aav vector-chromosome integration junctions from normal human fibroblasts and describe their genomic distribution. we found a si ... | 2005 | 16103194 |
| amelioration of laminin-alpha2-deficient congenital muscular dystrophy by somatic gene transfer of miniagrin. | congenital muscular dystrophy (cmd) is characterized by severe muscle wasting, premature death in early childhood, and lack of effective treatment. most of the cmd cases are caused by genetic mutations of laminin-alpha2, which is essential for the structural integrity of muscle extracellular matrix. here, we report that somatic gene delivery of a structurally unrelated protein, a miniature version of agrin, functionally compensates for laminin-alpha2 deficiency in the murine models of cmd. adeno ... | 2005 | 16103356 |
| noninvasive monitoring of therapeutic gene transfer in animal models of muscular dystrophies. | muscular dystrophies are a genetically and phenotypically heterogeneous group of degenerative muscle diseases. a subset of them are due to genetic deficiencies in proteins which form the dystrophin-associated complex at the membrane of the myofibers. in this report, we utilized recombinant adeno-associated virus containing a u7 cassette carrying an antisense sequence aimed at inducing exon skipping of the dystrophin gene or containing the alpha-sarcoglycan gene to alleviate the dystrophic phenot ... | 2006 | 16107863 |
| [the construction of recombinant aav vector expressing hsvtk gene controlled by tet-on and the detection of its activity]. | in order to investigate the application of recombinant adeno-associated virus (raav) vector containing tet regulation system and hsvtk gene in cancer gene therapy, paav/tre/hsvtk/tet-on was constructed and identified with pcr and restriction enzyme digestion. packaging cells hek293 were cotransfected with plasmids paav/tre/hsvtk/tet-on, paav-rc and paav-helper to produce infectious raav, and cscl2 densitygradient centrifugation method was performed for purification and concentration of raav. the ... | 2005 | 16108356 |
| long-term safety of gdnf gene delivery in the retina. | to examine retinal function after the long-term, gene therapy-delivered expression of exogenous glial cell line-derived neurotrophic factor (gdnf). | 2005 | 16109652 |
| adeno-associated virus and lentivirus pseudotypes for lung-directed gene therapy. | the enthusiasm for cystic fibrosis gene therapy that attended the initial cloning of the gene and in vitro correction of the genetic defect eventually diminished as we learned more about the limitations of vector technologies that were available in the 1980s and 1990s. substantial progress has been made, however, over the last 5 years in developing second- and third-generation vector constructs that should be more useful in achieving gene transfer to the lung for the treatment of pulmonary disea ... | 2004 | 16113451 |
| adeno-associated virus vector-mediated systemic delivery of ifn-beta combined with low-dose cyclophosphamide affects tumor regression in murine neuroblastoma models. | type i ifns (ifn-alpha/beta) have shown significant antitumor activity in preclinical models but limited efficacy and significant toxicity in clinical trials. we hypothesized that the antitumor activity of type i ifns could be enhanced by chronic, low-dose systemic delivery and sought to test this in murine neuroblastoma models. | 2005 | 16115947 |
| 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- ... | 2005 | 16116646 |
| targeted expression of igf-1 in the central nervous system fails to protect mice from experimental autoimmune encephalomyelitis. | insulin-like growth factor 1 (igf-1) has been identified as a critical molecule in the induction of myelination in the central nervous system (cns). systemic injection of igf-1 has been shown to have a varied and transiently protective effect on the clinical course of experimental autoimmune encephalomyelitis (eae). since systemic igf-1 can also modulate peripheral immune lymphocytes, we examined whether a sustained and local delivery of igf-1 into the spinal cord would have any influence on the ... | 2005 | 16120466 |
| gene replacement therapy rescues photoreceptor degeneration in a murine model of leber congenital amaurosis lacking rpgrip. | retinitis pigmentosa gtpase regulator (rpgr) is a photoreceptor protein anchored in the connecting cilia by an rpgr-interacting protein (rpgrip). loss of rpgrip causes leber congenital amaurosis (lca), a severe form of photoreceptor degeneration. the current study was an investigation of whether somatic gene replacement could rescue degenerating photoreceptors in a murine model of lca due to a defect in rpgrip. | 2005 | 16123399 |
| establishment of effective methods for transducing genes into iris pigment epithelial cells by using adeno-associated virus type 2. | to establish an efficient method of transferring the human brain-derived neurotrophic-factor (hbdnf) gene into human iris pigment epithelial (hipe) cells by using recombinant adeno-associated virus type 2 (raav2). | 2005 | 16123438 |
| systemic overexpression of interleukin-10 fails to protect allogeneic islet transplants in nonobese diabetic mice. | interleukin (il)-10 has proven effective in various allogeneic transplantation models and for preventing recurrent autoimmune rejection of syngeneic islets in nod mice. therefore, we evaluated systemic il-10 overexpression on allogeneic islet graft survival. diabetic nod mice received a single injection of recombinant adeno-associated virus (raav) serotype 2 encoding murine il-10 (raav-il-10) four weeks prior to renal subcasular islet transplantation. in a model having both autoimmune and alloge ... | 2005 | 16123729 |
| gene-transfer technology: a preventive neurotherapy to curb obesity, ameliorate metabolic syndrome and extend life expectancy. | leptin insufficiency at crucial target sites in the hypothalamic circuitries that integrate energy intake and expenditure underlies abnormal rates of fat accumulation. the payload of this "fat burden" is metabolic syndrome, a cluster of life-threatening metabolic afflictions, and a shorter lifespan. currently available therapies employed to combat obesity have disadvantages such as poor compliance for lifestyle modification or transient effectiveness and undesirable side-effects of pharmacologic ... | 2005 | 16125798 |
| utility of pegylated recombinant adeno-associated viruses for gene transfer. | adeno-associated virus (aav), capable of producing significant, long-term transgene expression, is one of the least toxic vectors employed in pre-clinical and clinical studies of gene transfer. one limitation is generation of neutralizing antibodies against viral capsids, blocking gene expression after readministration. aav2 capsids were modified with poly(ethylene) glycols (pegs) activated by cyanuric chloride (ccpeg), succinimidyl succinate (sspeg) and tresyl chloride (tmpeg). sspeg and tmpeg ... | 2005 | 16125817 |
| 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 ... | 2005 | 16129416 |
| enhanced transduction of mouse bone marrow-derived dendritic cells by repetitive infection with self-complementary adeno-associated virus 6 combined with immunostimulatory ligands. | the potential of adeno-associated virus (aav)-based vectors in human gene therapy is being explored for several diseases. although sustained transgene expression and low vector-associated cellular immunity are attractive features of recombinant (r) aav, the wider application of raav vectors encapsidated in serotype 2 capsid is hampered by poor transduction efficiency in many target tissues. these include ex vivo-generated dendritic cells (dc), which have demonstrated promising immunotherapeutic ... | 2006 | 16136165 |
| green fluorescent protein-tagged adeno-associated virus particles allow the study of cytosolic and nuclear trafficking. | to allow the direct visualization of viral trafficking, we genetically incorporated enhanced green fluorescent protein (gfp) into the adeno-associated virus (aav) capsid by replacement of wild-type vp2 by gfp-vp2 fusion proteins. high-titer virus progeny was obtained and used to elucidate the process of nuclear entry. in the absence of adenovirus 5 (ad5), nuclear translocation of aav capsids was a slow and inefficient process: at 2 h and 4 h postinfection (p.i.), gfp-vp2-aav particles were found ... | 2005 | 16140755 |
| adeno-associated virus-mediated gene transfer of a secreted form of trail inhibits tumor growth and occurrence in an experimental tumor model. | tumor necrosis factor-related apoptosis-inducing ligand (trail) induces cell death in various tumor cells, but relatively spares normal cells. recombinant adeno-associated virus (raav) vectors have a number of advantages including in vivo long-term gene expression. here, we assessed the biological activity of a novel, secreted form of trail (strail) for cancer gene therapy using a raav2 vector. | 2006 | 16144019 |
| knockdown of wild-type mouse rhodopsin using an aav vectored ribozyme as part of an rna replacement approach. | to develop a hammerhead ribozymes (rz) that might be exploited in a "digest and replace" gene therapy strategy for autosomal dominant retinitis pigmentosa (adrp) caused by mutations in the gene for rhodopsin (rho). | 2005 | 16145542 |
| confronting the issues of therapeutic misconception, enrollment decisions, and personal motives in genetic medicine-based clinical research studies for fatal disorders. | genetic medicine-based therapies have unlocked the potential for ameliorating diseases previously considered inevitably fatal. inherent in the clinical trials of genetic medicines are ethical issues of therapeutic misconception, enrollment decisions as they relate to the risks and benefits of research, and the complex relationships among funding sources, investigators, and the families of affected individuals. the purpose of this paper is to help define these complex issues relevant to the use o ... | 2005 | 16149901 |
| tetracycline-inducible viral interleukin-10 intraocular gene transfer, using adeno-associated virus in experimental autoimmune uveoretinitis. | members of the adeno-associated virus (aav) family are good candidates for the treatment of ocular diseases because of their relative lack of pathogenicity. we studied the effect of intraocular injection of aav2-viral il-10 (vil-10) on retinal s-antigen-induced experimental autoimmune uveoretinitis (eau) in lewis rats. we demonstrated that aav2/2-gfp injected into the vitreous body transduced the iris and ciliary body, or anterior uvea, and the retina. we showed that intravitreal injection of th ... | 2005 | 16149902 |
| genomic stability of self-complementary adeno-associated virus 2 during early stages of transduction in mouse muscle in vivo. | studies have demonstrated that packaging of recombinant adeno-associated virus 2 (raav) as self-complementary duplex strand (sc) results in early transgene expression, possibly eliminating rate-limiting second-strand synthesis. in the present study, we evaluated the molecular organization, stability of the sc aav genome, and transgene expression in the quadriceps muscle of c57bl/6j mice in vivo as compared with single-stranded (ss) aav. studies were carried out with raav encoding green fluoresce ... | 2005 | 16149903 |
| spliceosome-mediated rna trans-splicing with recombinant adeno-associated virus partially restores cystic fibrosis transmembrane conductance regulator function to polarized human cystic fibrosis airway epithelial cells. | we previously reported that spliceosome-mediated rna trans-splicing (smart), using recombinant adenoviral vectors expressing pre-trans-splicing molecules (ptms), could partially restore cystic fibrosis transmembrane conductance regulator (cftr) chloride channel activity to polarized human deltaf508 cf airway epithelia. although these studies proved that smart could correct cftr mrna defects, recombinant adenoviral infection from the basolateral surface was required because of inefficient infecti ... | 2005 | 16149910 |
| reversal of gene expression profile in the phenylketonuria mouse model after adeno-associated virus vector-mediated gene therapy. | phenylketonuria (pku) is an autosomal recessive metabolic disorder caused by phenylalanine hydroxylase (pah) deficiency. accumulation of phenylalanine leads to severe mental and psychomotor retardation, and hypopigmentation of skin and hair. we have demonstrated the cognitive outcome of biochemical and phenotypic reversal by the adeno-associated virus vector-mediated gene delivery of a human pah transgene. in this study, we identified the expression of genes related to pathologic abnormalities o ... | 2005 | 16150627 |
| preferential expression of an aav-2 construct in nos-positive interneurons following intrastriatal injection. | most cns studies using recombinant adeno-associated virus type 2 (raav-2) vectors have focused on gene delivery for the purpose of gene therapy. in the present study, we examined the feasibility of using raav-2 vectors to study the regulation of preprotachykinin-a (ppt-a) promoter activity in striatal medium spiny projection neurons. an raav-2 vector incorporating a ppt promoter fragment (shown previously to confer some cell-specificity of expression in vitro) coupled to a green fluorescent prot ... | 2005 | 16153741 |
| 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 ... | 2005 | 16157771 |
| how adeno-associated virus rep78 protein arrests cells completely in s phase. | adeno-associated virus rep78 protein has antiproliferative effects on cells. it inhibits cell cycle progression, and, in particular, rep78 induces a complete arrest within s phase, a response rarely seen after cell dna damage. we examined how rep78 achieves such an efficient s phase block. rep78 inhibits cdc25a activity by a novel means in which binding between the two proteins stabilizes cdc25a, thus increasing its abundance, while at the same time preventing access to its substrates cyclin-dep ... | 2005 | 16157891 |
| four-dimensional visualization of the simultaneous activity of alternative adeno-associated virus replication origins. | the adeno-associated virus (aav) inverted terminal repeats (itrs) contain the aav rep protein-binding site (rbs) and the terminal resolution site (trs), which together act as a minimal origin of dna replication. the aav p5 promoter also contains an rbs, which is involved in rep-mediated regulation of promoter activity, as well as a functional trs, and origin activity of these signals has in fact been demonstrated previously in the presence of adenovirus helper functions. here, we show that in th ... | 2005 | 16160148 |
| isolation, characterization, gene modification, and nuclear reprogramming of porcine mesenchymal stem cells. | bone marrow mesenchymal stem cells (mscs) are adult pluripotent cells that are considered to be an important resource for human cell-based therapies. understanding the clinical potential of mscs may require their use in preclinical large-animal models, such as pigs. the objectives of the present study were 1) to establish porcine msc (pmsc) cultures; 2) to optimize in vitro pmsc culture conditions, 3) to investigate whether pmscs are amenable to genetic manipulation, and 4) to determine pmsc rep ... | 2006 | 16162872 |
| [viral vectors in gene therapy. advantages of the adenoassociated vectors]. | gene therapy has evolved due to the development of a number of biotechnology weapons, i.e., vectors that achieve for a longer expression and safer administration. among viral vectors developed adeno-associated virus have shown promising advantages. these dna viruses transduce a wide cell range, can integrate in host's genome and achieve for a long-period expression, besides avoiding a cellular immune response. the new technologies applied to the production and purification of these vectors had r ... | 2005 | 16167495 |
| specific and efficient transduction of cochlear inner hair cells with recombinant adeno-associated virus type 3 vector. | recombinant adeno-associated virus (aav) vectors are of interest for cochlear gene therapy because of their ability to mediate the efficient transfer and long-term stable expression of therapeutic genes in a wide variety of postmitotic tissues with minimal vector-related cytotoxicity. in the present study, seven aav serotypes (aav1-5, 7, 8) were used to construct vectors. the expression of egfp by the chicken beta-actin promoter associated with the cytomegalovirus immediate-early enhancer in coc ... | 2005 | 16169458 |
| gene therapy with human osteoprotegerin decreases callus remodeling with limited effects on biomechanical properties. | osteoprotegerin (opg) is a naturally occurring protein, which prevents bone resorption by inhibition of osteoclastogenesis, function, and survival. therefore, recombinant opg may be an attractive drug in the treatment of chronic bone resorptive diseases such as osteoporosis. gene therapy has the potential to achieve long-term treatment by delivering genes of anti-resorptive proteins to the recipient. the effects of opg gene therapy on fracture healing have not been described previously. the infl ... | 2005 | 16169783 |
| [immunostimulatory effect of human peripheral blood dendritic cells transfected by adeno-associated virus containing her2/neu gene]. | to observe the immunostimulatory effect of human peripheral blood dendritic cells (dcs) transfected by her2/neu gene delivered by adeno-associated virus. | 2005 | 16174595 |
| transduction of pancreatic islets with pseudotyped adeno-associated virus: effect of viral capsid and genome conversion. | recombinant adeno-associated viral (raav) vectors currently show promise for islet gene therapy. in the presence of complementing aav2 rep proteins, aav2 genomes can be packaged with other serotype capsids to assemble infectious virions. during transduction, the ssdna to dsdna conversion is one of the major rate-limiting steps that contribute to the slow onset of transgene expression. | 2005 | 16177645 |
| inhibition of ovarian cancer metastasis by adeno-associated virus-mediated gene transfer of nm23h1 in an orthotopic implantation model. | ovarian cancer is one of the most threatening malignant tumors in females due to the frequent occurrence of metastasis that precedes diagnosis. the present study explored the possibility of preventing ovarian cancer metastasis by promoting nm23h1 expression through adeno-associated virus (aav)-mediated gene transfer. a cell line of high metastatic potential, sw626-m4, was derived by in vivo selection and used to establish an ovarian cancer metastasis model in the mouse. liver metastasis and anim ... | 2006 | 16179930 |
| viral-mediated temporally controlled dopamine production in a rat model of parkinson disease. | regulation of gene expression is necessary to avoid possible adverse effects of gene therapy due to excess synthesis of transgene products. to reduce transgene expression, we developed a viral vector-mediated somatic regulation system using inducible cre recombinase. a recombinant adeno-associated virus (aav) vector expressing cre recombinase fused to a mutated ligand-binding domain of the estrogen receptor alpha (creer(t2)) was delivered along with aav vectors expressing dopamine-synthesizing e ... | 2006 | 16182609 |
| improved survival of ischemic cutaneous and musculocutaneous flaps after vascular endothelial growth factor gene transfer using adeno-associated virus vectors. | a major challenge in reconstructive surgery is flap ischemia, which might benefit from induction of therapeutic angiogenesis. here we demonstrate the effect of an adeno-associated virus (aav) vector delivering vascular endothelial growth factor (vegf)165 in two widely recognized in vivo flap models. for the epigastric flap model, animals were injected subcutaneously with 1.5 x 10(11) particles of aav-vegf at day 0, 7, or 14 before flap dissection. in the transverse rectus abdominis musculocutane ... | 2005 | 16192634 |
| current development of adeno-associated viral vectors. | vectors based on adeno-associated virus (aav) have recently been used in phase i clinical trials for the treatment of neurological disorders, such as parkinson's and canavan's diseases. indeed, aav-mediated gene transfer is a promising tool for the delivery of therapeutic gene into the central and peripheral nervous systems. aav-mediated gene transfer was also applied in phase i and phase ii clinical trials for the treatment of cystic fibrosis and in phase i clinical trials for the treatment of ... | 2005 | 16193103 |
| species-specific differences in mouse and human airway epithelial biology of recombinant adeno-associated virus transduction. | differences in airway epithelial biology between mice and humans have presented challenges to evaluating gene therapies for cystic fibrosis (cf) using murine models. in this context, recombinant adeno-associated virus (raav) type 2 and raav5 vectors have very different transduction efficiencies in human air-liquid interface (ali) airway epithelia (raav2 approximately = raav5) as compared with mouse lung (raav5 >> raav2). it is unclear if these differences are due to species-specific airway biolo ... | 2006 | 16195538 |
| long-term correction of murine glycogen storage disease type ia by recombinant adeno-associated virus-1-mediated gene transfer. | glycogen storage disease type ia (gsd-ia) is caused by a deficiency in glucose-6-phosphatase-alpha (g6pase-alpha), a nine-transmembrane domain, endoplasmic reticulum-associated protein expressed primarily in the liver and kidney. previously, we showed that infusion of an adeno-associated virus (aav) serotype 2 vector carrying murine g6pase-alpha (aav2-g6pase-alpha) into neonatal gsd-ia mice failed to sustain their life beyond weaning. we now show that neonatal infusion of gsd-ia mice with an aav ... | 2006 | 16195703 |
| attachment of adeno-associated virus type 3h to fibroblast growth factor receptor 1. | heparan sulfate proteoglycan is thought to act as primary receptor for adeno-associated virus type 2 (aav-2). reported coreceptors include alphavbeta5 integrin, fibroblast growth factor receptor 1 (fgfr-1), and hepatocyte growth factor (c-met). the interaction of aav type 3 (aav-3) with possible cell membrane receptors is incompletely defined. in this study, using assays detecting competition with viral infection, virus binding inhibition assays and dot blotting, we show attachment of aav-3 stra ... | 2006 | 16195782 |
| a proximal e-box modulates ngf effects on rat ppt-a promoter activity in cultured dorsal root ganglia neurones. | the rat preprotachykinin a (rtppta) promoter fragment spanning -865+92, relative to the major transcriptional start, has previously been demonstrated to be nerve growth factor (ngf) responsive in primary cultures of rat dorsal root ganglion (drg) neurones [harrison, p.t., dalziel, r.g., ditchfield, n.a., quinn, j.p., 1999. neuronal-specific and nerve growth factor-inducible expression directed by the preprotachykinin-a promoter delivered by an adeno-associated virus vector. neuroscience 94, 997- ... | 2005 | 16198417 |
| multiple human papillomavirus genes affect the adeno-associated virus life cycle. | the risk of cervical cancer, one of the most prevalent cancers in the world, is determined by two viruses. human papillomavirus (hpv) is the main risk factor for developing cervical cancer. however, although little known, it is well substantiated that the human parvovirus adeno-associated virus type 2 (aav), and its encoded rep78 protein, interacts with hpv and lowers the risk of cervical cancer. hpv also contributes to aav inhibition by serving as a helper virus for aav and stimulating higher a ... | 2006 | 16203022 |
| hypothalamic pro-opiomelanocortin gene delivery ameliorates obesity and glucose intolerance in aged rats. | age-related obesity is associated with impaired hypothalamic pro-opiomelanocortin (pomc) gene expression. we assessed whether overproduction of pomc in the hypothalamus ameliorates age-related obesity in rats. | 2005 | 16205885 |
| large-scale production of recombinant viruses by use of a large culture vessel with active gassing. | adenovirus and adeno-associated virus (aav) vectors are increasingly used for gene transduction experiments. however, to produce a sufficient amount of these vectors for in vivo experiments requires large-capacity tissue culture facilities, which may not be practical in limited laboratory space. we describe here a large-scale method to produce adenovirus and aav vectors with an active gassing system that uses large culture vessels to process labor- and cost-effective infection or transfection in ... | 2005 | 16218782 |
| adeno-associated virus inverted terminal repeats improve neuronal transgene expression mediated by baculoviral vectors in rat brain. | baculoviral vectors can transduce neurons in the cns but mediate only transient expression of transgenes. we have developed a new baculoviral vector in which the inverted terminal repeats (itrs) of adeno-associated virus are used to flank a luciferase reporter gene cassette harboring a neuron-specific promoter. when tested in rat brain, the new viral vector was able to provide transgene expression for at least 90 days. immunohistological analysis demonstrated that itr flanking did not affect the ... | 2005 | 16218783 |
| functional correction of cns phenotypes in a lysosomal storage disease model using adeno-associated virus type 4 vectors. | lysosomal storage diseases (lsds) represent a significant portion of inborn metabolic disorders. more than 60% of lsds have cns involvement. lsd therapies for systemic diseases have been developed, but efficacy does not extend to the cns. in this study, we tested whether adeno-associated virus type 4 (aav4) vectors could mediate global functional and pathological improvements in a murine model of mucopolysaccharidosis type vii (mps vii) caused by beta-glucuronidase deficiency. recombinant aav4 v ... | 2005 | 16221840 |
| glucose transporter-2 (glut2) promoter mediated transgenic insulin production reduces hyperglycemia in diabetic mice. | insulin production afforded by hepatic gene therapy (hgt) retains promise as a potential treatment for type 1 diabetes, but successful approaches have been limited. we employed a novel and previously untested promoter for this purpose, glucose transporter-2 (glut2) to drive insulin production via delivery by recombinant adeno-associated virus (raav). in vitro, the glut2 promoter was capable of robust glucose-responsive expression in transduced hepg2 human hepatoma cells. therefore, raav construc ... | 2005 | 16223491 |
| determination of osteoprogenitor-specific promoter activity in mouse mesenchymal stem cells by recombinant adeno-associated virus transduction. | towards utilizing gene-targeted, repopulating mesenchymal stem cells (msc) to increase osteogenesis, we evaluated the expression of bone-specific promoters during msc differentiation. multi-lineage potential of cultured msc was confirmed by osteogenic, adipogenic and chondrogenic differentiation under controlled conditions. recombinant adeno-associated virus (raav) encoding luciferase under the human cytomegalovirus (cmv), mouse alkaline phosphatase (alp), runx-2/cbfa1 (runx), osteopontin (opn), ... | 2005 | 16225939 |
| gene therapy for patients with rheumatoid arthritis. | gene therapy seeks either to supply a missing or dysfunctional gene or to ensure continuous long-lasting production of a therapeutic protein. rheumatoid arthritis is a candidate for gene therapy, as the mechanisms leading to joint inflammation and destruction have been partly elucidated. nevertheless, several crucial questions need to be addressed. knowledge of the underlying pathophysiological mechanisms is needed to guide selection of the candidate gene. in the light of current data, tnf and i ... | 2006 | 16226478 |
| aav2/5-mediated ngf gene delivery protects septal cholinergic neurons following axotomy. | nerve growth factor (ngf) therapy has been proposed to treat cognitive impairments in aged patients including those with alzheimer's disease. various viral vectors, including adeno-associated virus serotype 2 (aav2), have been investigated for their ability to deliver ngf in brain. in this study, hybrid vectors (aav2/5) consisting of the genome of recombinant aav2 and the capsid of aav serotype 5 were evaluated for their ability to deliver ngf and green fluorescent protein (gfp) genes into brain ... | 2005 | 16226726 |
| sustained whole-body functional rescue in congestive heart failure and muscular dystrophy hamsters by systemic gene transfer. | the success of muscular dystrophy gene therapy requires widespread and stable gene delivery with minimal invasiveness. here, we investigated the therapeutic effect of systemic delivery of adeno-associated virus (aav) vectors carrying human delta-sarcoglycan (delta-sg) gene in to-2 hamsters, a congestive heart failure and muscular dystrophy model with a delta-sg gene mutation. | 2005 | 16230483 |
| current issues in adeno-associated viral vector production. | adeno-associated virus (aav) is currently one of the most promising systems for human gene therapy. numerous preclinical studies have documented the excellent safety profile of these vectors along with their impressive performances in their favored target, consisting of highly differentiated postmitotic tissues such as muscle, central nervous system and liver. clinical trials have been conducted confirming these data, but also emphasizing the requirement of further high-tech developments of the ... | 2005 | 16231056 |
| purification of adenovirus and adeno-associated virus: comparison of novel membrane-based technology to conventional techniques. | adenovirus (ad) and adeno-associated virus (aav) are efficient gene delivery systems; manipulation of the wild-type genome allows their use as vectors for the overexpression of desirable transgenes. generation and purification of such viral vectors can be labour intensive, costly and require specialized equipment, but a new generation of membrane-mediated ion exchange kits for purification of recombinant virus may facilitate this process. here, we examine the yields, transgene expression and pur ... | 2005 | 16231057 |
| efficiency of adeno-associated virus type-2 vectors in non-human primate schwann cells. | adult macaque schwann cells were infected using adeno-associated virus type-2-derived vectors expressing the green fluorescent protein reporter gene under the control of the cytomegalovirus, the hybrid cytomegalovirus-betaactin, the myelin basic protein or the tetracycline-inducible promoters. on the basis of green fluorescent protein expression, gene transfer efficiency was compared in resting and dividing conditions following or not following hydroxyurea or etoposide treatment. hydroxyurea all ... | 2005 | 16237322 |
| 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 ... | 2005 | 16243306 |
| efficient in vivo gene expression by trans-splicing adeno-associated viral vectors. | although adeno-associated virus (aav)-mediated gene therapy has been hindered by the small viral packaging capacity of the vector, trans-splicing aav vectors are able to package twice the size of the vector genome. unfortunately, the efficiency of current trans-splicing vectors is very low. here we show that rational design of the gene splitting site has a profound influence on trans-splicing vector-mediated gene expression. using mrna accumulation as a guide, we generated a set of efficient tra ... | 2005 | 16244658 |
| intrathecal gene transfer by adeno-associated virus for pain. | chronic pain is among the most prevalent medical problems, affecting more than half of patients with advanced cancer and many with other common diseases. current analgesics often fail to provide satisfactory symptom relief and frequently cause severe side effects. intrathecal (it) gene transfer is an attractive method for pain research in rodent models, because it allows targeting of a wide variety of secretable peptides and proteins to the spinal cord, an important neural center for the process ... | 2005 | 16248278 |
| human immunoglobulin inhibits liver transduction by aav vectors at low aav2 neutralizing titers in scid mice. | long-term cures of hemophilia b have been achieved using aav2 delivering the factor ix gene to the liver of adeno-associated virus (aav)-naive hemophilic animals. however, the clinical success of this approach requires overcoming pre-existing aav neutralizing antibodies prevalent in humans. to better define the inhibition of neutralizing antibodies on aav2-mediated liver transduction, we developed an in vivo passive immunity model. scid mice were first reconstituted to a defined neutralizing tit ... | 2006 | 16249376 |
| pharmacological and raav gene therapy rescue of visual functions in a blind mouse model of leber congenital amaurosis. | leber congenital amaurosis (lca), a heterogeneous early-onset retinal dystrophy, accounts for approximately 15% of inherited congenital blindness. one cause of lca is loss of the enzyme lecithin:retinol acyl transferase (lrat), which is required for regeneration of the visual photopigment in the retina. | 2005 | 16250670 |
| il-10 suppresses chemokines, inflammation, and fibrosis in a model of chronic renal disease. | il-10 is a pluripotent cytokine that plays a pivotal role in the regulation of immune and inflammatory responses. whereas short-term administration of il-10 has shown benefit in acute glomerulonephritis, no studies have addressed the potential benefits of il-10 in chronic renal disease. chronically elevated blood levels of il-10 in rats were achieved by administration of a recombinant adeno-associated virus serotype 1 il-10 (raav1-il-10) vector. control rats were given a similar dose of raav1-gf ... | 2005 | 16251240 |
| a novel role of circadian transcription factor dbp in hippocampal plasticity. | in neurons, a variety of extracellular stimuli are capable of inducing transcriptional events that underlie complex processes ranging from learning to disease. the mechanisms linking these long-lasting cellular modifications to behavior remain to be established. here, we show by microarray analysis that hippocampal activation of glucagon-like peptide-1 receptor (glp-1r), which is associated with improved learning and neuroprotection, results in suppression of the transcription factor dbp (albumi ... | 2006 | 16257226 |
| adeno-associated virus-mediated expression of vascular endothelial growth factor peptides inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy. | vascular endothelial growth factor (vegf) has been demonstrated to be a key stimulator of retinal neovascularization (nv), the most common cause of severe and progressive vision loss. in this study, we used a mouse model of oxygen-induced retinopathy (oir) to explore the potential of gene expression and secretion of short vegf peptides as a treatment. peptide-encoding fragments of exons 6 and 7 of the vegf gene were cloned into a recombinant adeno-associated virus (raav) vector. expression of ea ... | 2005 | 16259558 |
| 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 ... | 2005 | 16259561 |
| comparative efficacy of intratracheal adeno-associated virus administration to newborn rats. | transient local overexpression of genes that promote lung defense or repair may help to protect or promote alveolar development in premature neonates. we showed that the use of adenoviral vectors in neonates was limited by the induction of lung growth disorders. in the present work we compare the efficiency of gene transfer to the neonatal lung by three adeno-associated viral vectors: raav1, raav2, and raav5. transduction efficiency was first measured in vitro, by infecting a549 immortalized hum ... | 2005 | 16259563 |
| high levels of persistent expression of alpha1-antitrypsin mediated by the nonhuman primate serotype rh.10 adeno-associated virus despite preexisting immunity to common human adeno-associated viruses. | alpha1-antitrypsin (alpha1at) deficiency is a genetic disorder causing emphysema if serum alpha1at levels are <570 microg/ml. we have shown that intrapleural administration of an aav5alpha1at vector yielded persistent therapeutic alpha1at serum levels. since anti-aav2 and -aav5 antibodies prevalent in humans may limit the use of these common serotypes in gene therapy, we screened 25 aav vectors derived from humans and nonhuman primates for alpha1at expression following intrapleural administratio ... | 2006 | 16260185 |
| precise hit: adeno-associated virus in gene targeting. | vectors based on the adeno-associated virus (aav) have attracted much attention as potent gene-delivery vehicles, mainly because of the persistence of this non-pathogenic virus in the host cell and its sustainable therapeutic gene expression. however, virus infection can be accompanied by potentially mutagenic random vector integration into the genome. a novel approach to aav-mediated gene therapy based on gene targeting through homologous recombination allows efficient, high-fidelity, non-mutag ... | 2005 | 16261169 |
| identification of mouse aav capsid-specific cd8+ t cell epitopes. | adeno-associated virus has been developed for use as a gene transfer vector. to understand the impact of aav capsid-specific cd8(+) t cells on aav-mediated gene transfer, we identified cd8(+) t cell epitopes for aav-2 and aav-8 capsid in c57bl/6 (h-2(b) mhc haplotype) and balb/c (h-2(d) mhc haplotype) mice. mice of both the h-2(b) and the h-2(d) haplotypes recognized epitopes on aav-2 and aav-8 capsid. t cells from h-2(b) mice recognized an epitope that was conserved between aav-2 and aav-8 caps ... | 2005 | 16263332 |
| treatment with hydroxyurea and tyrphostin-1 significantly improves the transduction efficiency of recombinant adeno-associated viruses in human cancer cells. | to enhance the transduction efficiency (te) of a recombinant adeno-associated virus 2 (raav2) in human cancer cells, we examined the combined effects of various chemicals known to influence the raav2 transduction process at distinct steps. among the agents tested were trichostatin a, a histone deacetylase inhibitor, mg-132, a proteosome inhibitor, the genotoxic agents hydroxyurea, aphidicolin, etoposide and camptothecin, and tyrphostin-1, an epidermal growth factor receptor inhibitor. during or ... | 2005 | 16273241 |