Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
|---|
| [effect of secretory human calcitonin gene-related peptide recombinant aav on penile erection in streptozotocin-induced diabetic rat]. | to determine whether recombinant adeno-associated virus-mediated overexpression of hcgrp in the corpus cavernosum can affect the continuous production of hcgrp in the penile tissue and enhance erectile responses in stz-induced diabetic rats. | 2005 | 16281515 |
| molecular characterization of adeno-associated viruses infecting children. | although adeno-associated virus (aav) infection is common in humans, the biology of natural infection is poorly understood. since it is likely that many primary aav infections occur during childhood, we set out to characterize the frequency and complexity of circulating aav isolates in fresh and archived frozen human pediatric tissues. total cellular dna was isolated from 175 tissue samples including freshly collected tonsils (n = 101) and archived frozen samples representing spleen (n = 21), lu ... | 2005 | 16282478 |
| characterization of adeno-associated virus genomes isolated from human tissues. | infection with wild-type adeno-associated virus (aav) is common in humans, but very little is known about the in vivo biology of aav. on a molecular level, it has been shown in cultured cells that aav integrates in a site-specific manner on human chromosome 19, but this has never been demonstrated directly in infected human tissues. to that end, we tested 175 tissue samples for the presence of aav dna, and when present, examined the specific form of the viral dna. aav was detected in 7 of 101 to ... | 2005 | 16282479 |
| adenovirus, adeno-associated virus and kawasaki disease. | clinical similarities and shared seasonality suggested a relationship between adenovirus infection and kawasaki disease. we performed adenovirus serology and quantitative polymerase chain reaction for both adenovirus and adeno-associated virus in patients with acute kawasaki disease. no evidence was found to suggest a link between either virus and kawasaki disease. | 2005 | 16282942 |
| adeno-associated vector mediated gene transfer of transforming growth factor-beta1 to normal and osteoarthritic human chondrocytes stimulates cartilage anabolism. | the objective of the present study was to investigate whether cartilage anabolism in human primary osteoarthritic chondrocytes could be improved by adeno-associated virus (aav) vector-mediated gene transduction of transforming growth factor tgf-beta1 (tgf-beta1). a bi-cistronic aav-tgf-beta1-ires-egfp (aav-tgf-beta1) vector was generated and used for transduction of a normal human articular chondrocyte cell line (tst/ac62) and primary human osteoarthritic articular chondrocytes harvested from 8 ... | 2005 | 16284937 |
| combinatorial engineering of a gene therapy vector: directed evolution of adeno-associated virus. | viruses are being exploited as vectors to deliver therapeutic genetic information into target cells. the success of this approach will depend on the ability to overcome current limitations, especially in terms of safety and efficiency, through molecular engineering of the viral particles. | 2006 | 16285001 |
| an autoimmune domain-reduced hcv core gene remains effective in stimulating anti-core cytotoxic t lymphocyte activity. | chronic hepatitis c virus (hcv) infection cases resistant to conventional therapies might be treated by immunotherapy as cytotoxic t lymphocytes (ctl) are the main mechanism through which viral infections are cleared. the hcv core gene, with the highest homology between hcv types, deleted of its autoimmune-stimulating regions (pseudo-gor and pseudo-p450), may be an appropriate antigen for targeting hcv-infected cells. two recombinant adeno-associated virus (raav) vectors, carrying either the ful ... | 2006 | 16289277 |
| safety and efficacy of aav-mediated calpain 3 gene transfer in a mouse model of limb-girdle muscular dystrophy type 2a. | calpainopathy (limb-girdle muscular dystrophy type 2a, lgmd2a) is a recessive muscular disorder caused by deficiency in the calcium-dependent cysteine protease calpain 3. to date, no treatment exists for this disease. we evaluated the potential of recombinant adeno-associated virus (raav) vectors for gene therapy in a murine model for lgmd2a. to drive the expression of calpain 3, we used raav2/1 pseudotyped vectors and muscle-specific promoters to avoid calpain 3 cell toxicity. we report efficie ... | 2006 | 16290124 |
| inhibition of atherogenesis in ldlr knockout mice by systemic delivery of adeno-associated virus type 2-hil-10. | atherosclerosis is an inflammatory disease of the arteries. interleukin-10 (il-10) is known to be an anti-inflammatory cytokine which might be useful for counteracting the development of atherosclerosis. as long-term systemic cytokine delivery is prohibitively expensive, gene therapy might be a suitable approach. to test this idea, low-density lipoprotein receptor (ldlr) knockout mice were injected with recombinant adeno-associated virus type 2 (aav)/interleukin-10 virus or aav/granulocyte macro ... | 2006 | 16300768 |
| gene transfer of human acid sphingomyelinase corrects neuropathology and motor deficits in a mouse model of niemann-pick type a disease. | niemann-pick type a disease is a lysosomal storage disorder caused by a deficiency in acid sphingomyelinase (asm) activity. previously we showed that storage pathology in the asm knockout (asmko) mouse brain can be corrected by adeno-associated virus serotype 2 (aav2)-mediated gene transfer. the present experiment compared the relative therapeutic efficacy of different recombinant aav serotype vectors (1, 2, 5, 7, and 8) using histological, biochemical, and behavioral endpoints. in addition, we ... | 2005 | 16301517 |
| biological approaches to bone regeneration by gene therapy. | safe, effective approaches for bone regeneration are needed to reverse bone loss caused by trauma, disease, and tumor resection. unfortunately, the science of bone regeneration is still in its infancy, with all current or emerging therapies having serious limitations. unlike current regenerative therapies that use single regenerative factors, the natural processes of bone formation and repair require the coordinated expression of many molecules, including growth factors, bone morphogenetic prote ... | 2005 | 16304438 |
| adeno-associated virus-based gene therapy for inherited disorders. | adeno-associated virus vectors are capable of long-term gene transfer without obvious adverse effects in a number of animal models. over the last two decades, preclinical and early phase clinical trials in cystic fibrosis and alpha-1 antitrypsin deficiency were undertaken to test the feasibility of this approach. the results of those studies have been important since they have indicated that in vivo gene transfer is feasible and relatively safe. in addition, a number of key limitations to the cu ... | 2005 | 16306183 |
| novel caprine adeno-associated virus (aav) capsid (aav-go.1) is closely related to the primate aav-5 and has unique tropism and neutralization properties. | preexisting humoral immunity to adeno-associated virus (aav) vectors may limit their clinical utility in gene delivery. we describe a novel caprine aav (aav-go.1) capsid with unique biological properties. aav-go.1 capsid was cloned from goat-derived adenovirus preparations. surprisingly, aav-go.1 capsid was 94% identical to the human aav-5, with differences predicted to be largely on the surface and on or under the spike-like protrusions. in an in vitro neutralization assay using human immunoglo ... | 2005 | 16306595 |
| activators of viral gene expression in polarized epithelial monolayers identified by rapid-throughput drug screening. | epithelial polarity and tight junction formation limit the ability of adenovirus, retrovirus and adeno-associated virus (aav) to deliver and express virally encoded genes. using an extended half-life luciferase assay and high-throughput luminometry, we screened 23 000 compounds and natural product extracts as potentiators to overcome this barrier. seven strong activators were discovered (up to several hundred fold above control) and two of these exhibited spectrum of activity in multiple cell ty ... | 2006 | 16307002 |
| intracerebral adeno-associated virus-mediated gene transfer in rapidly progressive forms of metachromatic leukodystrophy. | metachromatic leukodystrophy (mld) is a neurodegenerative lysosomal disease caused by a defect of the enzyme arylsulfatase a (arsa) that disrupts the degradation of sulfatides (sulf) in neurons and glial cells. therapy for mld requires active production of arsa in the brain to prevent demyelination and neuronal damage, and efficient delivery of arsa to act faster than disease progression, particularly in the rapidly progressive late infantile form. we used an adeno-associated virus serotype 5 (a ... | 2006 | 16311251 |
| effects of epoxyeicosatrienoic acids on levels of enos phosphorylation and relevant signaling transduction pathways involved. | endothelial nitric oxide synthase (enos) is a key enzyme responsible for the regulation of vascular homeostasis. many humor factors and mechanical forces can affect enos activity via phosphorylation modification but the mechanisms involved vary with stimuli applied. we have demonstrated that cytochrome p450 (cyp) epoxygenase-dependent metabolites of arachidonic acid, epoxyeicosatrienoic acids (eets), can robustly up-regulate enos expression and its activity, however the relevant signaling pathwa ... | 2005 | 16315601 |
| oral adeno-associated virus-strail gene therapy suppresses human hepatocellular carcinoma growth in mice. | the extracellular domain of the tumor necrosis factor-related apoptosis-inducing ligand (strail) may function as a soluble cytokine to selectively kill various cancer cells without toxicity to most normal cells. we constructed a series of recombinant adeno-associated virus (aav) vectors expressing the extracellular domain of human trail fused with signal peptides of human insulin, interferon, human growth hormone, and serum albumin and designated them as aav-isn-t, aav-ifn-t, aav-hgh-t, and aav- ... | 2005 | 16317690 |
| virus-based therapies for colon cancer. | viral vectors are under development for anticancer therapy. as they can infect tumours and activate the immune system, viral vectors may directly destroy cancers (oncolysis), deliver genes with antitumour activity directly to the cancer cells, or act as cancer vaccines. better insights into the biology of the various vectors in use (e.g., poxvectors, adenovirus, adeno-associated virus, reovirus, newcastle disease virus) are making it possible to engineer viruses that are more tumour-specific, ef ... | 2005 | 16318426 |
| administration-route and gender-independent long-term therapeutic correction of phenylketonuria (pku) in a mouse model by recombinant adeno-associated virus 8 pseudotyped vector-mediated gene transfer. | phenylketonuria (pku) is an inborn error of metabolism caused by deficiency of the hepatic enzyme phenylalanine hydroxylase (pah) which leads to high blood phenylalanine (phe) levels and consequent damage of the developing brain with severe mental retardation if left untreated in early infancy. the current dietary phe restriction treatment has certain clinical limitations. to explore a long-term nondietary restriction treatment, a somatic gene transfer approach in a pku mouse model (c57bl/6-pahe ... | 2006 | 16319947 |
| complete correction of hyperphenylalaninemia following liver-directed, recombinant aav2/8 vector-mediated gene therapy in murine phenylketonuria. | novel recombinant adeno-associated virus vectors pseudotyped with serotype 8 capsid (raav2/8) have recently shown exciting promise as effective liver-directed gene transfer reagents. we have produced a novel liver-specific raav2/8 vector expressing the mouse phenylalanine hydroxylase (pah) cdna and have administered this vector to hyperphenylalaninemic pah-deficient pah(enu2) mice, a model of human phenylketonuria (pku). our hypothesis was that this vector would produce sufficient hepatocyte tra ... | 2006 | 16319949 |
| [gene transfer patterns and transduction efficacy of recombinant adeno-associated virus type 1, 2, and 5 in brain: an experiment with rats]. | to investigate the gene transfer patterns and transduction efficacy of different serotypes of recombinant adeno-associated virus (raav): raav1, 2, and 5 in brain. | 2005 | 16321184 |
| self-complementary adeno-associated virus vectors containing a novel liver-specific human factor ix expression cassette enable highly efficient transduction of murine and nonhuman primate liver. | transduction with recombinant adeno-associated virus (aav) vectors is limited by the need to convert its single-stranded (ss) genome to transcriptionally active double-stranded (ds) forms. for aav-mediated hemophilia b (hb) gene therapy, we have overcome this obstacle by constructing a liver-restricted mini-human factor ix (hfix) expression cassette that can be packaged as complementary dimers within individual aav particles. molecular analysis of murine liver transduced with these self-compleme ... | 2006 | 16322469 |
| efficient neuronal gene transfer with aav8 leads to neurotoxic levels of tau or green fluorescent proteins. | adeno-associated virus (aav) serotype 8 appears to be the strongest of the natural serotypes reported to date for gene transfer in liver and muscle. in this study, we evaluated aav8 in the brain by several methods, including biophotonic imaging of green fluorescent protein (gfp). in the adult rat hippocampus, levels of gfp expressed were clearly greater with aav8 than with aav2 or aav5 by western blot and biophotonic imaging and slightly but significantly greater than aav1 by western blot. in th ... | 2006 | 16325474 |
| prevention and reversal of lupus in nzb/nzw mice by costimulatory blockade with adeno-associated virus-mediated gene transfer. | to investigate the potency of costimulatory blockade with adeno-associated virus (aav)-mediated gene transfer in the prevention and reversal of lupus in a murine model. | 2005 | 16329128 |
| [construction of recombinant adeno-associated virus vectors carrying double gene of antisense multidrug resistance-associated protein and antisense multidrug resistance]. | to construct a recombinant adeno-associated virus vectors carrying double gene of antisense multidrug resistance-associated protein (mrp) and antisense multidrug resistance (mdr1) for use in studying the gene therapy to reverse the multidrug resistance (mdr) in hepatocellular carcinoma (hcc). | 2005 | 16334547 |
| focal striatal dopamine may potentiate dyskinesias in parkinsonian monkeys. | striatal neurons convert l-dopa to dopamine (da) following gene transfer of aromatic l-amino acid decarboxylase (aadc) via adeno-associated virus (aav) in parkinsonian monkeys. we investigated whether aav-aadc could reduce or eliminate l-dopa-induced dyskinesias (lids) and side effects in mptp-treated monkeys. five monkeys were made parkinsonian by bilateral mptp lesions. the optimal therapeutic dose of l-dopa was determined using an acute dose response regimen. after 3 weeks of chronic l-dopa t ... | 2006 | 16337943 |
| enhanced transduction of mouse salivary glands with aav5-based vectors. | we previously demonstrated that recombinant adeno-associated virus vectors based on serotype 2 (raav2) can direct transgene expression in salivary gland cells in vitro and in vivo. however, it is not known how other raav serotypes perform when infused into salivary glands. the capsids of serotypes 4 and 5 are distinct from raav2 and from each other, suggesting that they may direct binding and entry into different cell types. in the present study, we investigated the tropisms, transduction effici ... | 2006 | 16341060 |
| tendon healing in vitro: bfgf gene transfer to tenocytes by adeno-associated viral vectors promotes expression of collagen genes. | adeno-associated virus-mediated gene transfer is promising in the delivery of genes to tendons because this vector stimulates few adverse tissue reactions. basic fibroblast growth factor (bfgf) promotes collagen production in healing tendons. we transferred the exogenous bfgf gene to proliferating tenocytes by adeno-associated viral (aav) vectors and investigated its effects on the expression of the collagen genes in an in vitro tenocyte model. | 2005 | 16344185 |
| analysis of adeno-associated virus and hpv interaction. | it is slowly becoming accepted that adeno-associated virus (aav) is another significant factor involved in cervical carcinogenesis. however, unlike human papillomavirus (hpv), which is positively associated with cervical cancer, aav is negatively associated with this cancer. this negative association appears to be through a direct and complex bi-directional interaction between aav and hpv. essentially all assays used for studying hpv can be used for studying the aav-hpv interaction. this is beca ... | 2005 | 16350413 |
| liver transduction with recombinant adeno-associated virus is primarily restricted by capsid serotype not vector genotype. | we and others have recently reported highly efficient liver gene transfer with adeno-associated virus 8 (aav-8) pseudotypes, i.e., aav-2 genomes packaged into aav-8 capsids. here we studied whether liver transduction could be further enhanced by using viral dna packaging sequences (inverted terminal repeats [itrs]) derived from aav genotypes other than 2. to this end, we generated two sets of vector constructs carrying expression cassettes embedding a gfp gene or the human factor ix (hfix) gene ... | 2006 | 16352567 |
| gene therapy strategies for duchenne muscular dystrophy utilizing recombinant adeno-associated virus vectors. | gene transfer vectors based on adeno-associated virus (aav) are now widely used in the field of gene therapy. these vectors have been studied for their potential use in treating many diseases, among them the muscular dystrophies, the most common of which is duchenne muscular dystrophy (dmd). several recent advances in the areas of aav serotype analysis, transgene engineering, and vector delivery to muscle, together with novel means of rescuing mutant mrna transcripts, have yielded impressive res ... | 2006 | 16361117 |
| viral gene therapy strategies: from basic science to clinical application. | a major impediment to the successful application of gene therapy for the treatment of a range of diseases is not a paucity of therapeutic genes, but the lack of an efficient non-toxic gene delivery system. having evolved to deliver their genes to target cells, viruses are currently the most effective means of gene delivery and can be manipulated to express therapeutic genes or to replicate specifically in certain cells. gene therapy is being developed for a range of diseases including inherited ... | 2006 | 16362990 |
| phenotype correction of hemophilia a mice with adeno-associated virus vectors carrying the b domain-deleted canine factor viii gene. | adeno-associated virus (aav) vectors carrying the b domain-deleted canine fviii (bdd cfviii) gene utilizing the beta-actin minimum promoter (167b) pseudotyped with serotype 1 (aav1-beta-actin-cfviii) and serotype 8 (aav8-beta-actin-cfviii) were developed to express cfviii in hemophilia a mice. fviii clotting activities measured by the aptt method increased in hemophilia a mice with intramuscular injection of aav1-beta-actin-cfviii in a dose-dependent manner. therapeutic fviii levels (2.9+/-1.0%) ... | 2006 | 16371232 |
| impact of capsid conformation and rep-capsid interactions on adeno-associated virus type 2 genome packaging. | single-stranded genomes of adeno-associated virus (aav) are packaged into preformed capsids. it has been proposed that packaging is initiated by interaction of genome-bound rep proteins to the capsid, thereby targeting the genome to the portal of encapsidation. here we describe a panel of mutants with amino acid exchanges in the pores at the fivefold axes of symmetry on aav2 capsids with reduced packaging and reduced rep-capsid interaction. mutation of two threonines at the rim of the fivefold p ... | 2006 | 16378983 |
| mutations on the external surfaces of adeno-associated virus type 2 capsids that affect transduction and neutralization. | mutations were made at 64 positions on the external surface of the adeno-associated virus type 2 (aav-2) capsid in regions expected to bind antibodies. the 127 mutations included 57 single alanine substitutions, 41 single nonalanine substitutions, 27 multiple mutations, and 2 insertions. mutants were assayed for capsid synthesis, heparin binding, in vitro transduction, and binding and neutralization by murine monoclonal and human polyclonal antibodies. all mutants made capsid proteins within a l ... | 2006 | 16378984 |
| a histone deacetylase inhibitor enhances recombinant adeno-associated virus-mediated gene expression in tumor cells. | the transduction of cancer cells using recombinant adeno-associated virus (raav) occurs with low efficiency, which limits its utility in cancer gene therapy. we have previously sought to enhance raav-mediated transduction of cancer cells by applying dna-damaging stresses. in this study, we examined the effects of the histone deacetylase inhibitor fr901228 on tumor transduction mediated by raav types 2 and 5. fr901228 treatment significantly improved the expression of the transgene in four cancer ... | 2006 | 16387551 |
| vascular bed-targeted in vivo gene delivery using tropism-modified adeno-associated viruses. | virus-mediated gene delivery is restricted by the infectivity profile of the chosen vector. targeting the vascular endothelium via systemic delivery has been attempted using peptides isolated in vitro (using either phage or vector display) and implicit reliance on target receptor expression in vivo. this has limited application since endothelial cells in vitro and in vivo differ vastly in receptor profiles and because of the existence of complex endothelial "zip codes" in vivo. we therefore test ... | 2006 | 16387552 |
| repair of articular cartilage defect by intraarticular administration of basic fibroblast growth factor gene, using adeno-associated virus vector. | the objective of this study was to establish the potency of adeno-associated virus (aav) as a viral vector to transport the basic fibroblast growth factor (bfgf) gene into synovial tissue, and to evaluate the consequent repair of articular cartilage defects. in the in vitro study, lacz- and bfgf-encoding genes were transduced into rabbit synoviocytes by recombinant adeno-associated virus (aav) vector, and the cells were cultured for 2 weeks. the percentage of successfully transduced lacz-positiv ... | 2005 | 16390272 |
| elevated rhoa/rho-kinase activity in the aged rat penis: mechanism for age-associated erectile dysfunction. | epidemiologic studies have shown that aging accounts significantly for the prevalence of erectile dysfunction (ed). the pathophysiology of ed during aging and its underlying molecular mechanisms are largely unknown. we hypothesized that increased rhoa/rho-kinase signaling is a major factor in the pathogenesis of age-associated ed and the mechanism involves increased penile smooth muscle contractility through inhibition of myosin light chain phosphatase. male fischer 344 young (4 month old) and a ... | 2006 | 16396994 |
| [expression and effect of hcgrp recombinant adeno-associated virus in primary cultured corporal cavernosum smooth muscle cells of the rat in vitro]. | to observe the expression and effect of human calcitonin gene-related peptide (hcgrp) gene mediated by recombinant adeno-associated virus (raav) in primary cultured corporal cavernosum smooth muscle cells of the rat and explore the possibility of using cgrp gene for gene therapy in erectile dysfunction. | 2005 | 16398364 |
| the distribution, concentration, and toxicity of enhanced green fluorescent protein in retinal cells after genomic or somatic (virus-mediated) gene transfer. | the concentration of enhanced green fluorescent protein (egfp) in individual photoreceptor cells of live mouse retina was quantified and correlated with physiological measurements of cell function. | 2005 | 16402024 |
| distribution of aav2-haadc-transduced cells after 3 years in parkinsonian monkeys. | the present report describes for the first time, the stability of recombinant adeno-associated virus serotype 2 (aav2) human aromatic l-amino acid decarboxylase (haadc) gene transfer after 3-year survival time in a non-human primate model of parkinson's disease. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys were treated with six injections of 30 microl/site of aav2-haadc at a concentration of 2 x 10(12) vg/ml into the caudate and putamen. stereological analysis revealed a 46.6% i ... | 2006 | 16407771 |
| adeno-associated virus types 5 and 6 use distinct receptors for cell entry. | the transduction efficiency of adeno-associated virus (aav) vectors in various somatic tissues is determined primarily by the viral capsid proteins. in contrast to vectors made with aav type 2 capsids, those having type 5 or 6 capsids show high transduction rates in airway epithelial cells, in a range that should be sufficient for treating lung disease. here we have compared the properties of vectors made with aav5 or aav6 capsid proteins to determine whether their receptor usage is similar, and ... | 2006 | 16409121 |
| efficient aav1-aav2 hybrid vector for gene therapy of hemophilia. | adeno-associated virus (aav) serotype 1 (aav1) has been shown to be more effective than the well-studied aav serotype 2 (aav2) in muscle gene transfer. replacement of amino acids 350 to 430 of aav2 vp1 with the corresponding amino acids from vp1 of aav1 resulted in a hybrid vector, termed aav-221-iv, which behaved similarly to aav1 in vitro and in vivo in muscle. intramuscular injection of 1x10(11) vector particles per mouse of hybrid vector carrying a human fix transgene in cd4 knockout mice re ... | 2006 | 16409124 |
| systemic correction of a fatty acid oxidation defect by intramuscular injection of a recombinant adeno-associated virus vector. | mitochondrial beta-oxidation of fatty acids is required to meet physiologic energy requirements during illness and periods of fasting or physiologic stress, and is most active in liver and striated muscle. acyl-coa dehydrogenases of varying chain-length specificities represent the first step in the mitochondria for each round of beta-oxidation, each of which removes two-carbon units as acetyl-coa for entry into the tricarboxylic acid cycle. we have used recombinant adeno-associated virus (raav) ... | 2006 | 16409126 |
| recombinant adeno-associated viral vectors as therapeutic agents to treat neurological disorders. | recombinant adeno-associated virus (raav) is derived from a small human parvovirus with an excellent safety profile. in addition, this viral vector efficiently transduces and supports long-term transgene expression in the nervous system. these properties make raav a reasonable candidate vector for treating neurological disorders. indeed, raav is currently being used in five early stage clinical trials for various neurodegenerative disorders. therefore, we will review the currently available prec ... | 2006 | 16412695 |
| transduction characteristics of adeno-associated virus vectors expressing cap serotypes 7, 8, 9, and rh10 in the mouse brain. | recombinant adeno-associated viral (aav) vectors can transduce cells of the cns, resulting in long-term expression. aav vector transduction varies depending on the serotype used and the region of the brain injected. aav serotypes 7, 8, 9, and rh10 have recently become available, but the transduction capabilities of these serotypes within the cns have not been determined. we show that aav 7, 8, 9, and rh10 vectors expressing cdna for a lysosomal enzyme transduce neurons, but not astrocytes or oli ... | 2006 | 16413228 |
| adeno-associated virus vectors serotyped with aav8 capsid are more efficient than aav-1 or -2 serotypes for widespread gene delivery to the neonatal mouse brain. | adeno-associated virus (aav) vectors have gained a preeminent position in the field of gene delivery to the normal brain through their ability to achieve extensive transduction of neurons and to mediate long-term gene expression with no apparent toxicity. in adult animals direct infusion of aav vectors into the brain parenchyma results in highly efficient transduction of target structures. however aav-mediated global delivery to the adult brain has been an elusive goal. in contrast, widespread g ... | 2006 | 16414198 |
| directed evolution of adeno-associated virus yields enhanced gene delivery vectors. | adeno-associated viral vectors are highly safe and efficient gene delivery vehicles. however, numerous challenges in vector design remain, including neutralizing antibody responses, tissue transport and infection of resistant cell types. changes must be made to the viral capsid to overcome these problems; however, very often insufficient information is available for rational design of improvements. we therefore applied a directed evolution approach involving the generation of large mutant capsid ... | 2006 | 16429148 |
| efficient site-specific integration of large transgenes by an enhanced herpes simplex virus/adeno-associated virus hybrid amplicon vector. | we previously demonstrated that a herpes simplex virus type 1 (hsv-1)/adeno-associated virus (aav) hybrid amplicon vector constructed by inserting the sequences of regulatory protein (rep) and inverted terminal repeats of aav into an hsv amplicon vector resulted in the enhanced stability of transgene expression compared to the original hsv-1 amplicon vector. however, problems related to the expression of rep compromised its therapeutic applications. we report here a new hsv/aav hybrid amplicon v ... | 2006 | 16439524 |
| scalable generation of high-titer recombinant adeno-associated virus type 5 in insect cells. | we established a method for production of recombinant adeno-associated virus type 5 (raav5) in insect cells by use of baculovirus expression vectors. one baculovirus harbors a transgene between the inverted terminal repeat sequences of type 5, and the second expresses rep78 and rep52. interestingly, the replacement of type 5 rep52 with type 1 rep52 generated four times more raav5 particles. we replaced the n-terminal portion of type 5 vp1 with the equivalent portion of type 2 to generate infecti ... | 2006 | 16439543 |
| raav2 traffics through both the late and the recycling endosomes in a dose-dependent fashion. | inefficient trafficking of recombinant adeno-associated virus type-2 (raav2) to the nucleus is a major barrier for transduction. using imaging and subcellular fractionation techniques, we evaluated the extent of raav2 movement through the late (rab7) and recycling (rab11) endosomes. following raav2 infection of hela cells, immunoisolation of ha-rab7- or ha-rab11-tagged endosomes and intracellular colocalization of cy3-labeled raav2 with egfp-rab7 or egfp-rab11 markers demonstrated dose-dependent ... | 2006 | 16442847 |
| protection from the toxicity of diisopropylfluorophosphate by adeno-associated virus expressing acetylcholinesterase. | organophosphorus esters (op) are highly toxic chemicals used as pesticides and nerve agents. their acute toxicity is attributed to inhibition of acetylcholinesterase (ache, ec 3.1.1.7) in nerve synapses. our goal was to find a new therapeutic for protection against op toxicity. we used a gene therapy vector, adeno-associated virus serotype 2 (aav-2), to deliver murine ache to ache-/- mice that have no endogenous ache activity. the vector encoded the most abundant form of ache: exons 2, 3, 4, and ... | 2006 | 16443250 |
| transduction of myogenic cells by retargeted dual high-capacity hybrid viral vectors: robust dystrophin synthesis in duchenne muscular dystrophy muscle cells. | duchenne muscular dystrophy (dmd) is caused by mutations in the dystrophin gene (dmd), making it amenable to gene- or cell-based therapies. another possible treatment entails the combination of both principles by transplantation of autologous myogenic cells after their genetic complementation. this approach requires efficient and stable transduction of these cells with recombinant dmd. recently, we generated a dual high-capacity (hc) adenovirus (ad)-adeno-associated virus (aav) hybrid vector (hv ... | 2006 | 16443396 |
| development of anticancer gene vaccine interact with human papillomavirus oncoprotein inhibition. | adeno-associated virus (aav) rep 78 protein is known to inhibit the promoter site of several oncogenes and viral genes, including the human papillomavirus (hpv) type 16 e6 transforming genes. the biochemical studies of rep 78 have been reported, but the effects of rep 78 gene-mediated inhibition of hpv 16 e6 promoter activity on the various human cervical carcinoma cells have not been characterized. pegfp-n1 vector, cloned by aav-mediated rep 78, is transfected into cervical carcinoma cells. tra ... | 2006 | 16445644 |
| intrathecal long-term gene expression by self-complementary adeno-associated virus type 1 suitable for chronic pain studies in rats. | intrathecal (it) gene transfer is an attractive approach for targeting spinal mechanisms of nociception but the duration of gene expression achieved by reported methods is short (up to two weeks) impairing their utility in the chronic pain setting. the overall goal of this study was to develop it gene transfer yielding true long-term transgene expression defined as > or = 3 mo following a single vector administration. we defined "it" administration as atraumatic injection into the lumbar cerebro ... | 2006 | 16445862 |
| [abeta vaccine therapy for alzheimer's disease]. | in 1999, schenk et al reported that vaccination of pdapp-transgenic mice with synthetic abeta42 in complete freund's adjuvant showed markedly decrease of the amyloid burden in the brain. the second trial of vaccine, an1792, for alzheimer's patients was halted because of meningoencephalitis found in 6% of patients and one autopsy case was reported. here, we comment the methods and the immunological mechanisms of abeta vaccine therapy and discuss the pathological changes in the brain and side effe ... | 2005 | 16447748 |
| improved cardiac gene transfer by transcriptional and transductional targeting of adeno-associated viral vectors. | vectors based on recombinant adeno-associated virus 2 (aav-2) are a promising tool for cardiac gene transfer. however, potential therapeutic applications need to consider the predominant transduction of the liver once aav-2 vectors enter the systemic circulation. we therefore aimed to increase efficiency and specificity of cardiac vector delivery by combining transcriptional and cell surface targeting. | 2006 | 16448634 |
| heme oxygenase-1 (ho-1) inhibits postmyocardial infarct remodeling and restores ventricular function. | we reported previously that predelivery of the anti-oxidant gene heme oxygenase-1 (ho-1) to the heart by adeno associated virus (aav) markedly reduces injury after acute myocardial infarction (mi). however, the effect of ho-1 gene delivery on postinfarction recovery has not been investigated. in the current study, we assessed the effect of ho-1 gene delivery on post-mi left ventricle (lv) remodeling and function using echocardiographic imaging and histomorphometric approaches. two groups of spra ... | 2006 | 16449792 |
| intracranial delivery of cln2 reduces brain pathology in a mouse model of classical late infantile neuronal ceroid lipofuscinosis. | classical late infantile neuronal ceroid lipofuscinosis (clincl) is a lysosomal storage disorder caused by mutations in cln2, which encodes lysosomal tripeptidyl peptidase i (tpp1). lack of tpp1 results in accumulation of autofluorescent storage material and curvilinear bodies in cells throughout the cns, leading to progressive neurodegeneration and death typically in childhood. in this study, we injected adeno-associated virus (aav) vectors containing the human cln2 cdna into the brains of cln2 ... | 2006 | 16452657 |
| gene therapy progress and prospects--vectorology: design and production of expression cassettes in aav vectors. | adeno-associated virus (aav) derived vectors are considered highly eligible vehicles for human gene therapy. not only do they possess many great potential for clinical applications due to their wide range of tissue targets but also their excellent preclinical safety profile makes them particularly suitable candidates for treating serious diseases. initial clinical trials have yielded encouraging results and prompted further improvements in their design and methods of production. many studies hav ... | 2006 | 16453010 |
| genetically modified dendritic cells for cancer immunotherapy. | the ability to grow and differentiate dendritic cells (dc) ex vivo has allowed their genetic manipulation to enhance immune activation against tumor antigens. gene engineering of dc can be achieved with a variety of physical methods and using different viral vectors. rna or dna transfection, either alone (naked), coated with liposomes or using electroporation or gene guns leads to t cell activation while transgene expression is frequently undetectable. adenoviral and retroviral vectors have prov ... | 2005 | 16457651 |
| chronic recurrent myocardial ischemic injury is significantly attenuated by pre-emptive adeno-associated virus heme oxygenase-1 gene delivery. | we assessed the hypothesis that overexpression of the antioxidant enzyme heme oxygenase (ho)-1 may protect against chronic recurrent ischemia/reperfusion injury. | 2006 | 16458149 |
| down-regulation of alpha-synuclein expression can rescue dopaminergic cells from cell death in the substantia nigra of parkinson's disease rat model. | fibrillization and aggregation of alpha-synuclein may play a critical role in neurodegenerative diseases like parkinson's diseases. adeno-associated virus (aav) vector delivery of an alpha-synuclein ribozyme was tested for its silencing effect on degenerating nigrostriatal neurons in the mpp(+) model of parkinson's disease. we designed alpha-synuclein ribozyme against human alpha-synuclein gene expression and constructed alpha-synuclein ribozymes-carrying raav vector (designated raav-synrz). co- ... | 2006 | 16460685 |
| [expression of coagulation factor ix in human cd34 + hematopoietic stem cells by adeno-associated virus 2]. | to investigate the expression of human coagulation factor ix (hfix) gene in human umbilical cord blood (cb) cd34+ cells which was transfected with recombinant adeno-associated virus 2 (raav-2). | 2005 | 16468329 |
| vegf, a mediator of the effect of experience on hippocampal neurogenesis. | rodents housed in an enriched environment, exercise by running or perform learning and memory tasks show an increase in hippocampal neurogenesis. we show that both environmental enrichment, as well as performance in the morris water maze, a hippocampal-dependent learning task, leads to an increase in local vegf expression in rats. we genetically recreated this situation by somatic cell gene transfer using recombinant adeno-associated virus (aav) vectors. genetically increasing hippocampal vegf i ... | 2006 | 16472200 |
| evaluation of a novel short polyadenylation signal as an alternative to the sv40 polyadenylation signal. | the soluble neuropilin-1 (snrp-1) gene employs an extremely short dual function polyadenylation (pa) signal/stop codon that is efficient for termination of gene transcription and translation in vivo. however, the functionality and usefulness of this signal in regard to other genes is unknown. this quantitative study compares the levels of humanized renilla green fluorescent protein (hrgfp) mrna polyadenylated with either the snrp-1 pa signal or the much larger, more widely used sv40 pa signal. w ... | 2006 | 16472858 |
| removal of empty capsids from type 1 adeno-associated virus vector stocks by anion-exchange chromatography potentiates transgene expression. | production of recombinant adeno-associated virus (raav) results in substantial quantities of empty capsids or virus-like particles (vlps), virus protein shells without the vector genome. the contaminating vlps would interfere with transduction by competing for cell-surface receptors and, when administered in vivo, contribute to antigen load, which may elicit a stronger immune response. density-gradient ultracentrifugation provides a means to separate vlps from raav particles, but is not feasible ... | 2006 | 16473554 |
| mosaic vectors comprised of modified aav1 capsid proteins for efficient vector purification and targeting to vascular endothelial cells. | vascular-targeted gene therapies have the potential to treat many of the leading causes of mortality in the western world. unfortunately, these therapies have been ineffective due to poor vascular gene transfer. the use of alternative virus serotypes and the incorporation of vascular targeting ligands into vectors has resulted in only modest increases in vascular gene transfer. adeno-associated virus (aav) 1 has shown the most promise among the aav vectors for the transduction of vascular endoth ... | 2006 | 16482202 |
| intrathecal administration of aav vectors for the treatment of lysosomal storage in the brains of mps i mice. | mucopolysaccharidosis type i (mps i) is caused by an inherited deficiency of alpha-l-iduronidase (idua). the result is a progressive, lysosomal storage disease with central nervous system (cns) as well as systemic involvement. to target gene therapy to the cns, recombinant adeno-associated virus (aav) vectors carrying idua sequence were administered to mps i mice via injection into cerebrospinal fluid. in contrast to intravenous administration, this intrathecal administration was effective in ge ... | 2006 | 16482204 |
| extracellular signal-regulated kinases 1/2 are required for adult retinal ganglion cell axon regeneration induced by fibroblast growth factor-2. | the intracellular signaling mechanisms used by neurotrophic factors to promote axon growth in the mature, injured central nervous system are not well understood. here we investigated the signaling cascades that control fibroblast growth factor-2 (fgf-2)-mediated retinal ganglion cell (rgc) axon extension in vivo. for this purpose, a novel adeno-associated virus (aav) was used to deliver the fgf-2 gene to rgcs, providing a sustained source of this neurotrophic factor. fgf-2 gene transfer led to a ... | 2006 | 16493686 |
| intranasal vaccination with recombinant adeno-associated virus type 5 against human papillomavirus type 16 l1. | adeno-associated viruses (aav) have been developed and evaluated as recombinant vectors for gene therapy in many preclinical studies, as well as in clinical trials. however, only a few approaches have used recombinant aav (raav) to deliver vaccine antigens. we generated an raav encoding the major capsid protein l1 (l1h) from the human papillomavirus type 16 (hpv16), aiming to develop a prophylactic vaccine against hpv16 infections, which are the major cause of cervical cancer in women worldwide. ... | 2006 | 16501072 |
| gene therapy as a therapeutic approach for the treatment of rheumatoid arthritis: innovative vectors and therapeutic genes. | in recent years, significant progress has been made in the treatment of rheumatoid arthritis (ra). in addition to conventional therapy, novel biologicals targeting tumour necrosis factor-alpha have successfully entered the clinic. however, the majority of the patients still has some actively inflamed joints and some patients suffer from side-effects associated with the high systemic dosages needed to achieve therapeutic levels in the joints. in addition, due to of the short half-life of these pr ... | 2006 | 16510530 |
| freeze-thaw increases adeno-associated virus transduction of cells. | a combination of gene and cell-based therapies may provide significant advantages over existing treatments in terms of their effectiveness. however, long-term efficient gene delivery has been difficult to achieve in many cell types, including endothelial cells. we developed a freeze-thaw technique which significantly increases the transduction efficiency of recombinant adeno-associated virus vectors in human aortic endothelial cells (23-fold) and in human renal proximal tubular epithelial cells ... | 2006 | 16510845 |
| production, purification, crystallization and preliminary x-ray analysis of adeno-associated virus serotype 8. | adeno-associated viruses (aavs) are actively being developed for clinical gene-therapy applications and the efficiencies of the vectors could be significantly improved by a detailed understanding of their viral capsid structures and the structural determinants of their tissue-transduction interactions. aav8 is approximately 80% identical to the more widely studied aav2, but its liver-transduction efficiency is significantly greater than that of aav2 and other serotypes. the production, purificat ... | 2005 | 16511095 |
| production, purification, crystallization and preliminary x-ray structural studies of adeno-associated virus serotype 5. | adeno-associated virus serotype 5 (aav5) is under development for gene-therapy applications for the treatment of cystic fibrosis. to elucidate the structural features of aav5 that control its enhanced transduction of the apical surface of airway epithelia compared with other aav serotypes, x-ray crystallographic studies of the viral capsid have been initiated. the production, purification, crystallization and preliminary crystallographic analysis of empty aav5 viral capsids are reported. the cry ... | 2005 | 16511195 |
| a novel antiapoptotic role for alpha1-antitrypsin in the prevention of pulmonary emphysema. | there is growing evidence that alveolar cell apoptosis plays an important role in emphysema pathogenesis, a chronic inflammatory lung disease characterized by alveolar destruction. the association of alpha1-antitrypsin deficiency with the development of emphysema has supported the concept that protease/antiprotease imbalance mediates cigarette smoke-induced emphysema. | 2006 | 16514110 |
| a 16bp rep binding element is sufficient for mediating rep-dependent integration into aavs1. | adeno-associated virus (aav) is a non-pathogenic virus and the only known eukaryotic virus capable of targeting human chromosome 19 for integration at a well-characterized aavs1 site. its site-specific integration is mediated by rep68 and rep78, viral proteins that bind to both the viral genome and aavs1 site on ch19 through a specific rep-binding element (rbe) located in both the viral genome and aavs1. there are three rbes in the aav genome: two identical ones in both inverted terminal repeats ... | 2006 | 16516232 |
| therapeutic level of functional human alpha 1 antitrypsin (haat) secreted from murine muscle transduced by adeno-associated virus (raav1) vector. | alpha 1 antitrypsin (aat) is a serine proteinase inhibitor (serpin). one well-known function of this protein is to inactivate neutrophil elastase and other neutrophil-derived proteinases, and prevent the destruction of pulmonary extracellular matrix. deficiency of aat can cause emphysema due to degradation of interstitial elastin by elastase. the majority of circulating aat is secreted from the liver. muscle-directed gene therapy using recombinant adeno-associated virus 2 (raav2) vectors has bee ... | 2006 | 16518879 |
| gene transfer into rat mesenchymal stem cells: a comparative study of viral and nonviral vectors. | mesenchymal stem cells (mscs) have been proposed for use in combinatorial gene and cell therapy protocols for the treatment of disease and promotion of repair. the efficacy of such a therapeutic approach depends on determination of which vectors give maximal transgene expression with minimal cell death. the study was carried out on bone-marrow derived rat mscs, and a range of vectors was tested on the same stem cell preparation. adenovirus, adeno-associated virus (aav; serotypes 1, 2, 4, 5, and ... | 2006 | 16522166 |
| restoration of fatty aldehyde dehydrogenase deficiency in sjögren-larsson syndrome. | sjögren-larsson syndrome (sls) is an autosomal recessive neurocutaneous disorder caused by mutation in the aldh3a2 gene that codes for human fatty aldehyde dehydrogenase (faldh). sjögren-larsson syndrome patients lack faldh, which catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acids. the impaired faldh activity leads to congenital ichthyosis, mental retardation and spasticity. the current lack of treatment is an impetus to develop gene therapy strategies by introducing functi ... | 2006 | 16525484 |
| apobec3a is a potent inhibitor of adeno-associated virus and retrotransposons. | apobec3 proteins constitute a family of cytidine deaminases that provide intracellular resistance to retrovirus replication and transposition of endogenous retroelements. one family member, apobec3a (ha3a), is an orphan, without any known antiviral activity. we show that ha3a is catalytically active and that it, but none of the other family members, potently inhibits replication of the parvovirus adeno-associated virus (aav). ha3a was also a potent inhibitor of the endogenous ltr retroelements, ... | 2006 | 16527742 |
| raav-mediated shrna ameliorated neuropathology in huntington disease model mouse. | huntington disease (hd) is a fatal progressive neurodegenerative disorder associated with expansion of a cag repeat in the first exon of the gene coding the protein huntingtin (htt). although the feasibility of rna interference (rnai)-mediated reduction of htt expression to attenuate hd-associated symptoms is suggested, the effects of post-symptomatic rnai treatment in the hd model mice have not yet been certified. here we show the effects of recombinant adeno-associated virus (raav)-mediated de ... | 2006 | 16530728 |
| immune responses to aav in a phase i study for canavan disease. | canavan disease is a rare leukodystrophy with no current treatment. raav-aspa has been developed for gene delivery to the central nervous system (cns) for canavan disease. this study represents the first use of a viral vector in an attempt to ameliorate a neurodegenerative disorder. | 2006 | 16532510 |
| recombinant adeno-associated virus-mediated inhibiting of interleukin-4 expression in rat model of asthma. | 2006 | 16537009 | |
| somatic gene transfer of camp response element-binding protein attenuates memory impairment in aging rats. | camp response element-binding protein (creb) is important for the formation and facilitation of long-term memory in diverse models. however, to our knowledge, involvement of creb in age-associated memory impairment has not been reported. here, we use a recombinant adeno-associated virus vector to obtain stable transgenic expression of creb as well as the inducible camp early repressor (icer) in the hippocampus of adult rats. in a longitudinal study, we show that somatic gene transfer of both cre ... | 2006 | 16537429 |
| impact of the interaction between herpes simplex virus type 1 regulatory protein icp0 and ubiquitin-specific protease usp7 on activation of adeno-associated virus type 2 rep gene expression. | expression of the herpes simplex virus type 1 (hsv-1) regulatory protein icp0 in transfected cells reactivates rep gene expression from integrated adeno-associated virus (aav) type 2 genomes via a mechanism that requires both its ring finger and usp7 interaction domains. in this study, we found that the rep reactivation defect of usp7-binding-negative icp0 mutants can be overcome by further deletion of sequences in the c-terminal domain of icp0, indicating that binding of usp7 to icp0 is not dir ... | 2006 | 16537633 |
| recombinant aav-mediated hsvtk gene transfer with direct intratumoral injections and tet-on regulation for implanted human breast cancer. | hsvtk/ganciclovir (gcv) gene therapy has been extensively studied in tumors and relies largely on the gene expression of hsvtk. most studies, however, have failed to demonstrate any significant benefit of a controlled gene expression strategy in cancer treatment. the tet-on system is commonly used to regulate gene expression following dox induction. we have evaluated the antitumor effect of hsvtk/ganciclovir gene therapy under tet-on regulation by means of adeno-associated virus-2 (aav-2)-mediat ... | 2006 | 16539746 |
| axons and synaptic boutons are highly dynamic in adult visual cortex. | while recent studies of synaptic stability in adult cerebral cortex have focused on dendrites, how much axons change is unknown. we have used advances in axon labeling by viruses and in vivo two-photon microscopy to investigate axon branching and bouton dynamics in primary visual cortex (v1) of adult macaque monkeys. a nonreplicative adeno-associated virus bearing the gene for enhanced green fluorescent protein (aav.egfp) provided persistent labeling of axons, and a custom-designed two-photon mi ... | 2006 | 16543135 |
| in vivo complementation of complex i by the yeast ndi1 enzyme. possible application for treatment of parkinson disease. | recent studies suggest that dysfunction of the nadh-quinone oxidoreductase (complex i) is associated with a number of human diseases, including neurodegenerative disorders such as parkinson disease. we have shown previously that the single subunit rotenone-insensitive nadh-quinone oxidoreductase (ndi1) of saccharomyces cerevisiae mitochondria can restore nadh oxidation in complex i-deficient mammalian cells. the ndi1 enzyme is insensitive to complex i inhibitors such as rotenone and 1-methyl-4-p ... | 2006 | 16543240 |
| adeno-associated virus-mediated transduction of vegf165 improves cardiac tissue viability and functional recovery after permanent coronary occlusion in conscious dogs. | we have previously shown that vegf165 gene delivery into ischemic skeletal muscle exerts not only proangiogenic, but also remarkable antiapoptotic and proregenerative activity. the aim of this study was to determine whether recombinant adeno-associated virus (raav)-mediated gene delivery of vegf165 into cardiac muscle, during acute myocardial infarction, exerts a protective effect to promote long-term functional recovery. acute infarction of the anterior lv wall was induced in 12 chronically ins ... | 2006 | 16543500 |
| convection-enhanced delivery of adeno-associated virus type 2 (aav2) into the striatum and transport of aav2 within monkey brain. | adeno-associated virus type 2 (aav2)-based vectors are promising transgene carriers for experimental gene therapy treatments of brain diseases. however, detailed evaluation of transgene distribution, trafficking, and transport within the brain is of the utmost importance before applying any type of gene therapy in humans. we examined the distribution of aav2-thymidine kinase (aav2-tk) and aav2-aromatic l-amino acid decarboxylase (aav2-aadc) in monkey brain after convection-enhanced delivery (ced ... | 2006 | 16544978 |
| evaluation of primitive murine hematopoietic stem and progenitor cell transduction in vitro and in vivo by recombinant adeno-associated virus vector serotypes 1 through 5. | conflicting data exist on hematopoietic cell transduction by aav serotype 2 (aav2) vectors, and additional aav serotype vectors have not been evaluated for their efficacy in hematopoietic stem/progenitor cell transduction. we evaluated the efficacy of conventional, single-stranded aav serotype vectors 1 through 5 in primitive murine hematopoietic stem/progenitor cells in vitro as well as in vivo. in progenitor cell assays using sca1+ c-kit+ lin- hematopoietic cells, 9% of the colonies in culture ... | 2006 | 16544981 |
| insertional mutagenesis at positions 520 and 584 of adeno-associated virus type 2 (aav2) capsid gene and generation of aav2 vectors with eliminated heparin- binding ability and introduced novel tropism. | recombinant adeno-associated virus (aav) vectors are promising in the context of gene therapy because of their ability to mediate efficient gene transfer and stable gene expression. aav2 uses heparin sulfate as its primary receptor, which is widely expressed on the various tissues and organs. this limits the application of aav2 in targeting specific tissues. to make an aav2 vector with modified tropism, we constructed various aav2 capsid mutants by inserting rgd-4c peptide at position 520 and/or ... | 2006 | 16544984 |
| different osteogenic potentials of recombinant human bmp-6 adeno-associated virus and adenovirus in two rat strains. | the osteogenic potential of aav5hbmp6 was compared with that of adhbmp6 in immunodeficient and immunocompetent rats. aav5hbmp6 (2.3 x 10(12) particles) and adhbmp6 (5 x 10(7) pfu) elicited viral antibody production in immunocompetent rats. among rats that received aav5hbmp6, the earliest time points at which the bone was visible under ct scanner were 30 days in 2-month-old sprague-dawley (sd) rats and 60 days in 18-month-old sd rats. the mean volumes of ectopic bone 90 days after viral injection ... | 2006 | 16548680 |
| parkin is protective for substantia nigra dopamine neurons in a tau gene transfer neurodegeneration model. | parkin is a ubiquitin ligase involved in the ubiquitin-proteasome system. elevating parkin expression in cells reduces markers of oxidative stress while blocking parkin expression increases oxidative stress. in parkin gene knock down mouse and fly models, mitochondria function is deficient. parkin is neuroprotective against a variety of toxic insults, while it remains unclear which of the above properties of parkin may mediate the protective actions. one of the models for which parkin is protect ... | 2006 | 16554120 |
| aav delivery of mineralocorticoid receptor shrna prevents progression of cold-induced hypertension and attenuates renal damage. | the aim of this study was to determine the effect of rna interference inhibition of mineralocorticoid receptor (mr) on cold-induced hypertension (cih) and renal damage. recombinant adeno-associated virus (aav) carrying short hairpin small interference (si)rna for mr (aav.mr-shrna) was constructed and tested for the ability to inhibit renal mr and to control cih. three groups of rats with cih received aav.mr-shrna (1.25 x 10(9) particles/rat, intravenous), aav carrying scrambled shrna (aav.contro ... | 2006 | 16554840 |
| [transduction efficiency of recombinant adeno-associated virus 2 in human bone marrow cd34+ hematopoietic stem/progenitor cells and mesenchyme stem cells]. | to investigate the transduction efficiency of recombinant adeno-associated virus 2 ( raav2) in human bone marrow cd34+ hematopoietic stem/progenitor cells and mesenchyme stem cells. | 2006 | 16562668 |
| gene therapeutic approaches-transfer in vivo. | osteoarthritis (oa) is common, debilitating, expensive, incurable and very difficult to treat. gene transfer to the synovial linings of affected joints is a promising strategy for achieving sustained, therapeutic, intraarticular concentrations of anti-arthritic gene products. this is not reasonably possible with existing, alternative technologies. the present review summarizes progress in achieving direct, in vivo intraarticular gene delivery and expression. numerous non-viral vectors have been ... | 2006 | 16563557 |
| c-terminal-truncated microdystrophin recruits dystrobrevin and syntrophin to the dystrophin-associated glycoprotein complex and reduces muscular dystrophy in symptomatic utrophin/dystrophin double-knockout mice. | c-terminal-truncated (deltac) microdystrophin is being developed for duchenne muscular dystrophy gene therapy. encouraging results have been achieved in the mdx mouse model. unfortunately, mdx mice do not display the same phenotype as human patients. evaluating deltac microdystrophin in a symptomatic model will be of significant relevance to human trials. utrophin/dystrophin double-knockout (u-dko) mice were developed to model severe dystrophic changes in human patients. in this study we evaluat ... | 2006 | 16563874 |