Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
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| characterization of the adenoassociated virus rep protein complex formed on the viral origin of dna replication. | interaction between the adenoassociated virus (aav) replication proteins, rep68 and 78, and the viral terminal repeats (trs) is mediated by a dna sequence termed the rep-binding element (rbe). this element is necessary for rep-mediated unwinding of duplex dna substrates, directs rep catalyzed cleavage of the aav origin of dna replication, and is required for viral transcription and proviral integration. six discrete rep complexes with the aav tr substrates have been observed in vitro, and cross- ... | 2003 | 12954205 |
| adeno-associated virus (aav) vectors achieve prolonged transgene expression in mouse myocardium and arteries in vivo: a comparative study with adenovirus vectors. | plasmid dna and adenovirus vectors currently used in cardiovascular gene therapy trials are limited by low efficiency and short-lived transgene expression, respectively. recombinant adeno-associated virus (aav) has recently emerged as an attractive vector for cardiovascular gene therapy. in the present study, we have compared aav and adenovirus vectors with respect to gene transfer efficiency and the duration of transgene expression in mouse hearts and arteries in vivo. aav vectors (titer: 5 x 1 ... | 2003 | 12957756 |
| efficient and long-term intracardiac gene transfer in delta-sarcoglycan-deficiency hamster by adeno-associated virus-2 vectors. | intracardiac gene transfer and gene therapy have been investigated with different vector systems. here we used adeno-associated virus (aav) vectors to deliver either a reporter gene or a therapeutic gene into the heart of golden syrian hamsters. the method of gene delivery was direct infusion of the aav2 vectors into the coronary artery ex vivo in a heterotopically transplanted heart. when an aav2 vector carrying the lac-z gene driven by cmv promoter was delivered into the heart of healthy hamst ... | 2003 | 12960970 |
| in vivo high-efficiency transcoronary gene delivery and cre-loxp gene switching in the adult mouse heart. | high-efficiency somatic gene transfer in adult mouse heart has not yet been achieved in vivo. here, we demonstrate high-efficiency in vivo transcoronary gene delivery to the adult murine myocardium using a catheter-based technique with recombinant adenovirus (adv) and adeno-associated virus (aav) vectors in normal and genetically engineered mice. the method involves immersion hypothermia followed by transient aortic and pulmonary artery occlusion with proximal intra-aortic segmental injection of ... | 2003 | 12960971 |
| comparative transductions of breast cancer cells by three dna viruses. | defining the ideal vectors to transduce breast cancer using viruses is currently under intense pre-clinical evaluation. our study constitutes the first direct comparison of the infection efficiencies of a human serotype 5 (ad5), a canine serotype 2 (cav-2) adenovirus, and a human serotype 2 adeno-associated virus (aav-2) in breast cancer cells. we observed an excellent infection efficiency for ad5 vector, whereas both cav-2 and aav-2 vectors lead to low infection of these cells. real-time pcr, f ... | 2003 | 13679075 |
| direct comparison of efficiency and stability of gene transfer into the mammalian heart using adeno-associated virus versus adenovirus vectors. | recent gene therapy strategies have relied on the use of adenovirus or plasmid as vehicles for gene delivery to the heart. these approaches have been limited by low transduction frequencies and transient transgene expression. we sought to determine whether adeno-associated virus produces more stable, higher efficiency gene expression in the rodent heart than did previous conventional methods. | 2003 | 14502138 |
| adeno-associated virus vector-mediated transduction in the cat brain. | adeno-associated virus (aav) vectors are capable of delivering a therapeutic gene to the mouse brain that can result in long-term and widespread protein production. however, the human infant brain is more than 1000 times larger than the mouse brain, which will make the treatment of global neurometabolic disorders in children more difficult. in this study, we evaluated the ability of three aav serotypes (1,2, and 5) to transduce cells in the cat brain as a model of a large mammalian brain. the hu ... | 2003 | 14502216 |
| identification of pdgfr as a receptor for aav-5 transduction. | understanding the process of vector transduction has important implications for the application and optimal use of a vector system for human gene therapy. recent studies with vectors based on adeno-associated virus type 5 (aav-5) have shown utility of this vector system in the lung, central nervous system, muscle and eye. to understand the natural tropism of this virus and to identify proteins necessary for aav-5 transduction, we characterized 43 cell lines as permissive or nonpermissive for aav ... | 2003 | 14502277 |
| junonia coenia densovirus-based vectors for stable transgene expression in sf9 cells: influence of the densovirus sequences on genomic integration. | the invertebrate parvovirus junonia coenia densovirus (jcdnv) shares similarities with terminal hairpins and nonstructural (ns) protein activities of adeno-associated virus (aav) despite their evolutionary divergence (b. dumas, m. jourdan, a. m. pascaud, and m. bergoin, virology, 191:202-222, 1992, and c. ding, m. urabe, m. bergoin, and r. m. kotin, j. virol. 76:338-345, 2002). we demonstrate here that persistent transgene expression in insect cells results from stable integration of transfected ... | 2003 | 14512554 |
| identification of a heparin-binding motif on adeno-associated virus type 2 capsids. | infection of cells with adeno-associated virus (aav) type 2 (aav-2) is mediated by binding to heparan sulfate proteoglycan and can be competed by heparin. mutational analysis of aav-2 capsid proteins showed that a group of basic amino acids (arginines 484, 487, 585, and 588 and lysine 532) contribute to heparin and hela cell binding. these amino acids are positioned in three clusters at the threefold spike region of the aav-2 capsid. according to the recently resolved atomic structure for aav-2, ... | 2003 | 14512555 |
| site-specific genomic strategies for gene therapy. | like any disease treatment, gene therapy should be safe and efficacious. safety can be addressed by directly correcting the defective gene itself or by ensuring that genomic integration of a transgene is site-specific. unfortunately, it has proven difficult to achieve this level of safety without a concomitant loss in efficiency of gene correction or insertion. in this review, recent research attempts to achieve efficient site-specific gene therapy, including strategies using targeted gene conve ... | 2003 | 14513680 |
| quantitative model demonstrating that recombinant adeno-associated virus and green fluorescent protein are non-toxic to the rat retina. | recombinant adeno-associated virus (raav) is one of the most promising recombinant viral vectors for delivering therapeutic agents to the retina. the present study aims to quantify any effect that an raav construct may have on the retina. to be able to use raav for therapeutic purposes, the potentially toxic effect of the vector and an associated green fluorescent protein (gfp) marker has to be investigated. | 2003 | 14516434 |
| the adeno-associated virus major regulatory protein rep78-c-jun-dna motif complex modulates ap-1 activity. | multiple epidemiologic studies show that adeno-associated virus (aav) is negatively associated with cervical cancer (cx ca), a cancer which is positively associated with human papillomavirus (hpv) infection. mechanisms for this correlation may be by rep78's (aav's major regulatory protein) ability to bind the hpv-16 p97 promoter dna and inhibit transcription, to bind and interfere with the functions of the e7 oncoprotein of hpv-16, and to bind a variety of hpv-important cellular transcription fa ... | 2003 | 14517094 |
| in utero recombinant adeno-associated virus gene transfer in mice, rats, and primates. | gene transfer into the amniotic fluid using recombinant adenovirus vectors was shown previously to result in high efficiency transfer of transgenes into the lungs and intestines. adenovirus mediated in utero gene therapy, however, resulted in expression of the transgene for less than 30 days. recombinant adenovirus associated viruses (raav) have the advantage of maintaining the viral genome in daughter cells thus providing for long-term expression of transgenes. | 2003 | 14519209 |
| [adeno-associated virus vector carrying human minidystrophin gene smcka3999 effectively ameliorates dystrophic pathology in mdx model mice]. | duchenne muscular dystrophy (dmd) is the most common and letal genetic skeletal muscle disorder, caused by recessive mutations in the dystrophin gene and no treatment is available. the present paper is aimed to study if recombinant adeno-associated virus vector (raav) mediated dystrophin minigene smcka3999 could effectively ameliorates dystrophic pathology in mdx model mice. | 2003 | 14521733 |
| reversal of diabetes in the rat by injection of hematopoietic stem cells infected with recombinant adeno-associated virus containing the preproinsulin ii gene. | to study the effect of injecting hematopoietic stem cells containing the preproinsulin gene ii (ri2) via recombinant adeno-associated virus (raav) into normal and streptozotocin-diabetic rats. | 2003 | 14526153 |
| dopamine-dependent neurodegeneration in rats induced by viral vector-mediated overexpression of the parkin target protein, cdcrel-1. | mutations in the parkin gene are linked to autosomal-recessive juvenile parkinsonism (ar-jp). parkin functions as a ubiquitin protein ligase in the degradation of several proteins, including the neuron-specific septin cdcrel-1. ar-jp-associated parkin mutations inhibit ubiquitination and degradation of cdcrel-1 and other parkin target proteins. here we show that recombinant adeno-associated virus-mediated cdcrel-1 gene transfer to the substantia nigra of rats results in a rapid onset (6-10 days) ... | 2003 | 14530399 |
| delivery of recombinant adeno-associated virus by jet injection. | the jet-injection technology was used for delivery of recombinant adeno-associated virus (raav). although aav-based vectors are an attractive tool in gene therapy, some methodological and technical problems of their targeted delivery remain to be solved. we tried to address some of these cell-targeting problems by using a new low-volume needleless injection device the swiss injector. first we tested, by electron microscopy, whether jet-injection would have any detrimental effect on raav particle ... | 2003 | 14532994 |
| infection efficiency of human and mouse embryonic stem cells using adenoviral and adeno-associated viral vectors. | human and mouse embryonic stem (es) cells have the capacity to differentiate into derivatives of all three germ layers, suggesting novel therapies for degenerative, metabolic, and traumatic disorders. es-based regenerative medicine will be further advanced by the development of reliable methods for transgene introduction and expression. here, we show infection of human and mouse embryonic stem (es) cells with two of the most popular vectors in gene transfer, adenovirus type 5 (ad5) and adeno-ass ... | 2003 | 12713701 |
| intravitreal gene therapy reduces lysosomal storage in specific areas of the cns in mucopolysaccharidosis vii mice. | the mucopolysaccharidoses (mpss) are lysosomal storage diseases resulting from impaired catabolism of sulfated glycosaminoglycans. mps vii mice lack lysosomal beta-glucuronidase (gusb) activity, leading to the accumulation of partially degraded chondroitin, dermatan, and heparan sulfates in most tissues. consequently, these mice develop most of the symptoms exhibited by human mps vii patients, including progressive visual and cognitive deficits. to investigate the effects of reducing lysosomal s ... | 2003 | 12716937 |
| delivering antisense telomerase rna by a hybrid adenovirus/ adeno-associated virus significantly suppresses the malignant phenotype and enhances cell apoptosis of human breast cancer cells. | activated telomerase is frequently detected in cancer cells and is able to maintain and stabilize the integrity of telomeres; it also contributes to unlimited divisions in cancer cells. recently, a new generation of selective anticancer strategies is under development targeting the blockage of telomerase activity either at the protein level or telomerase rna. here, we report suppression of the malignant phenotype by the expression of the full-length antisense human telomerase rna (htr) delivered ... | 2003 | 12717417 |
| adeno-associated virus-mediated aspartoacylase gene transfer to the brain of knockout mouse for canavan disease. | canavan disease (cd) is an autosomal recessive leukodystrophy caused by deficiency of aspartoacylase (aspa). deficiency of aspa leads to elevation of n-acetyl-l-aspartic acid (naa) in the brain and urine. to explore the feasibility of gene transfer to replace aspa in cd, we generated a knockout mouse and constructed an aav vector that encodes human aspa cdna (haspa) followed by green fluorescent protein (gfp) after an intraribosomal entry site. we injected cd mice with raav-haspa-gfp in the stri ... | 2003 | 12718900 |
| human gene targeting by adeno-associated virus vectors is enhanced by dna double-strand breaks. | the use of adeno-associated virus (aav) to package gene-targeting vectors as single-stranded linear molecules has led to significant improvements in mammalian gene-targeting frequencies. however, the molecular basis for the high targeting frequencies obtained is poorly understood, and there could be important mechanistic differences between aav-mediated gene targeting and conventional gene targeting with transfected double-stranded dna constructs. conventional gene targeting is thought to occur ... | 2003 | 12724413 |
| efficient gene targeting mediated by adeno-associated virus and dna double-strand breaks. | gene targeting is the in situ manipulation of the sequence of an endogenous gene by the introduction of homologous exogenous dna. presently, the rate of gene targeting is too low for it to be broadly used in mammalian somatic cell genetics or to cure genetic diseases. recently, it has been demonstrated that infection with recombinant adeno-associated virus (raav) vectors can mediate gene targeting in somatic cells, but the mechanism is unclear. this paper explores the balance between random inte ... | 2003 | 12724414 |
| induction of functional neovascularization by combined vegf and angiopoietin-1 gene transfer using aav vectors. | vectors based on the adeno-associated virus (aav) deliver therapeutic genes to muscle and heart at high efficiency and maintain transgene expression for long periods of time. here we report about the synergistic effect on blood vessel formation of aav vectors expressing the 165 aa isoform of vascular endothelial growth factor (vegf165), a powerful activator of endothelial cells, and of angiopoietin-1 (ang-1), which is required for vessel maturation. high titer aav-vegf165 and aav-ang-1 vector pr ... | 2003 | 12727107 |
| packaging of an aav vector encoding human acid alpha-glucosidase for gene therapy in glycogen storage disease type ii with a modified hybrid adenovirus-aav vector. | we have developed an improved method for packaging adeno-associated virus (aav) vectors with a replication-defective adenovirus-aav (ad-aav) hybrid virus. the aav vector encoding human acid alpha-glucosidase (hgaa) was cloned into an e1, polymerase/preterminal protein-deleted adenovirus, such that it is packaged as an ad vector. importantly, the ad-aav hybrid cannot replicate during aav vector packaging in 293 cells, because of deletion of polymerase/preterminal protein. the residual ad-aav in t ... | 2003 | 12727109 |
| rgd inclusion in vp3 provides adeno-associated virus type 2 (aav2)-based vectors with a heparan sulfate-independent cell entry mechanism. | recombinant adeno-associated virus (aav) has become an attractive vector system for a number of gene therapy paradigms. however, the utility of aav vectors is often limited by the absence of heparan sulfate proteoglycan (hspg), the virus's primary attachment receptor, on the desired target cell population. in order to achieve hspg-independent gene delivery, several groups have shown that the endogenous tropism of aav can be expand by genetically altering the viral capsid. however, the parameters ... | 2003 | 12727115 |
| incorporation of calcium phosphate enhances recombinant adeno-associated virus-mediated gene therapy in diabetic mice. | increased efficiency of transgene expression is desired for virus-mediated gene delivery. in the present study, we examined the effect of calcium phosphate (capi) on recombinant adeno-associated virus (raav)-mediated insulin therapy in diabetic animals. | 2003 | 12731090 |
| a dna vaccine containing inverted terminal repeats from adeno-associated virus increases immunity to hiv. | dna vaccines have been used to induce both humoral and cellular immune responses against infectious microorganisms. this study explores whether dna vaccine immunogenicity can be improved by introducing inverted terminal repeats (itrs) from adeno-associated virus (aav) into the regulatory region of the dna plasmid. | 2003 | 12731092 |
| prevention of chronic deterioration of heart allograft by recombinant adeno-associated virus-mediated heme oxygenase-1 gene transfer. | allograft deterioration is the major obstacle to organ transplantation as a long-term treatment of end-stage heart failure. in this study, we transduced the antioxidant gene, heme oxygenase-1 (ho-1), to heart grafts using a recombinant adeno-associated viral vector (raav) in a rat heart transplantation model and investigated its potentiality in prevention of chronic graft deterioration. | 2003 | 12732603 |
| enhancement of recombinant adeno-associated virus type 2-mediated transgene expression in a lung epithelial cell line by inhibition of the epidermal growth factor receptor. | recombinant adeno-associated viruses (raavs) have attracted considerable interest as gene delivery systems because they show long-term expression in vivo and transduce numerous cell types. limitations to successful gene transduction from raavs have prompted investigations of a variety of treatments to enhance transgene expression from raav vectors. tyrphostin-1, an epidermal growth factor receptor (egfr) tyrosine kinase inhibitor, dramatically enhances raav transgene expression. elegant studies ... | 2003 | 12743297 |
| immune responses to adeno-associated virus and its recombinant vectors. | recombinant adeno-associated virus (raav) vectors have emerged as highly promising for use in gene transfer for a variety of reasons, including lack of pathogenicity and wide host range. in addition, all virus-encoded genes have been removed from standard raav vectors, resulting in their comparatively low intrinsic immunogenicity. for gene replacement strategies, transgenes encoded by raav vectors may induce less robust host immune responses than other vectors in vivo. however, under appropriate ... | 2003 | 12756417 |
| immune response following intraocular delivery of recombinant viral vectors. | there has been significant progress in the last few years in demonstrating the utility of recombinant viral vectors in treating a variety of ocular diseases. the field has moved beyond 'proof-of-principle' and, in fact, has entered the phase where some of these vectors/paradigms are being or soon will be evaluated in human clinical trials. for this reason and also, to increase the understanding of immunological effects of transgenes/viral vectors on the eye, it is important to summarize what is ... | 2003 | 12756418 |
| the pyruvate dehydrogenase complex as a target for gene therapy. | here we review the rationale for considering the pyruvate dehydrogenase multienzyme complex (pdc) as a target for gene therapy for defects in mitochondrial energetics. pdc is entirely nuclear encoded and is situated in the mitochondrial inner membrane. the complex catalyzes the rate-determining step in aerobic carbohydrate metabolism and plays a critical role in the efficient conversion of substrate fuel into energy by cells. pdc activity is regulated in large part by reversible phosphorylation ... | 2003 | 12762482 |
| cloning of an avian adeno-associated virus (aaav) and generation of recombinant aaav particles. | recent studies have proposed that adeno-associated viruses (aavs) are not evolutionarily linked to other mammalian autonomous parvoviruses but are more closely linked to the autonomous parvoviruses of birds. to better understand the relationship between primate and avian aavs (aaavs), we cloned and sequenced the genome of an aaav (atcc vr-865) and generated recombinant aaav particles. the genome of aaav is 4,694 nucleotides in length and has organization similar to that of other aavs. the entire ... | 2003 | 12768000 |
| identification of amino acid residues in the capsid proteins of adeno-associated virus type 2 that contribute to heparan sulfate proteoglycan binding. | the adeno-associated virus type 2 (aav2) uses heparan sulfate proteoglycan (hspg) as its primary cellular receptor. in order to identify amino acids within the capsid of aav2 that contribute to hspg association, we used biochemical information about heparin and heparin sulfate, aav serotype protein sequence alignments, and data from previous capsid studies to select residues for mutagenesis. charged-to-alanine substitution mutagenesis was performed on individual residues and combinations of basi ... | 2003 | 12768018 |
| intraventricular brain injection of adeno-associated virus type 1 (aav1) in neonatal mice results in complementary patterns of neuronal transduction to aav2 and total long-term correction of storage lesions in the brains of beta-glucuronidase-deficient mice. | inherited metabolic disorders that affect the central nervous system typically result in pathology throughout the brain; thus, gene therapy strategies need to achieve widespread delivery. we previously found that although intraventricular injection of the neonatal mouse brain with adeno-associated virus serotype 2 (aav2) results in dispersed gene delivery, many brain structures were poorly transduced. this limitation may be overcome by using different aav serotypes because the capsid proteins us ... | 2003 | 12768022 |
| long-term expression of angiostatin suppresses metastatic liver cancer in mice. | metastatic liver cancer has a very poor prognosis and lacks effective therapy. anti-angiogenic therapies, which starve tumors of blood supply, have proven to be effective in preclinical models because tumor growth is angiogenesis dependent. however, long-term, high-level, and sustained expression of angiogenesis inhibitors, such as angiostatin, is necessary to prevent dormant tumors from becoming active again. to achieve this objective, we engineered a recombinant adeno-associated virus (aav) ve ... | 2003 | 12774025 |
| structure determination of adeno-associated virus 2: three complete virus particles per asymmetric unit. | the atomic structure of adeno-associated virus 2 (aav-2) has been determined to 3.0 a resolution. aav-2 crystallized in space group p1, with unit-cell parameters a = 249.7, b = 249.7, c = 644.8 a, alpha = 90.0, beta = 101.2, gamma = 120.0 degrees. the crystals contained three full virus particles in the asymmetric unit, allowing 180-fold non-crystallographic symmetry averaging. the particle orientations were determined using the self-rotation function and found to have similar but resolvably dif ... | 2003 | 12777756 |
| aav serotype 2 vectors preferentially integrate into active genes in mice. | recombinant adeno-associated virus serotype 2 (raav2) is a promising vector for gene therapy because it can achieve long-term stable transgene expression in animals and human subjects after direct administration of vectors into various target tissues. in the liver, although stable transgene expression primarily results from extrachromosomal vector genomes, a series of experiments has shown that vector genomes integrate into host chromosomes in hepatocytes at a low frequency. despite the low inte ... | 2003 | 12778174 |
| structural and functional neuroprotection in a rat model of huntington's disease by viral gene transfer of gdnf. | huntington's disease (hd) is an autosomal dominant disorder caused by an expanded polyglutamine (cag) tract at the it15 locus on chromosome 4. these excessive repeats lead to the degeneration of striatal and cortical neurons resulting in a devastating cognitive, psychiatric, and motor disorder for which no treatments are available. neurotrophic factors support the viability of striatal neurons suggesting that they might prevent the inevitable neural degeneration and its accompanying functional d ... | 2003 | 12781994 |
| recombinant adeno-associated virus serotype 4 mediates unique and exclusive long-term transduction of retinal pigmented epithelium in rat, dog, and nonhuman primate after subretinal delivery. | we previously described chimeric recombinant adeno-associated virus (raav) vectors 2/4 and 2/5 as the most efficient vectors in rat retina. we now characterize these two vectors carrying the cmv.gfp genome following subretinal injection in the wistar rat, beagle dog, and cynomolgus macaque. both serotypes displayed stable gfp expression for the duration of the experiment (6 months) in all three animal models. similar to the aav-2 serotype, aav-2/5 transduced both rpe and photoreceptor cells, wit ... | 2003 | 12788651 |
| helper virus-free, optically controllable, and two-plasmid-based production of adeno-associated virus vectors of serotypes 1 to 6. | we present a simple and safe strategy for producing high-titer adeno-associated virus (aav) vectors derived from six different aav serotypes (aav-1 to aav-6). the method, referred to as "hot," is helper virus free, optically controllable, and based on transfection of only two plasmids, i.e., an aav vector construct and one of six novel aav helper plasmids. the latter were engineered to carry aav serotype rep and cap genes together with adenoviral helper functions, as well as unique fluorescent p ... | 2003 | 12788658 |
| nuclear protein phosphatase-1 regulates hiv-1 transcription. | we recently reported that protein phosphatase 1 (pp1) dephosphorylates rna polymerase ii c-terminal repeats and regulates hiv-1 transcription in vitro. here we provide evidence that pp1 is also required for tat-induced hiv-1 transcription and for viral replication in cultured cells. inhibition of pp1 by overexpression of nuclear inhibitor of pp1 (nipp1) inhibited tat-induced hiv-1 transcription in transient transfection assays. a mutant of nipp1 that was defective in binding to pp1 did not have ... | 2003 | 12788939 |
| preclinical in vivo evaluation of pseudotyped adeno-associated virus vectors for liver gene therapy. | we report the generation and use of pseudotyped adeno-associated viral (aav) vectors for the liver-specific expression of human blood coagulation factor ix (hfix). therefore, an aav-2 genome encoding the hfix gene was cross-packaged into capsids of aav types 1 to 6 using efficient, large-scale technology for particle production and purification. in immunocompetent mice, the resultant vector particles expressed high hfix levels ranging from 36% (aav-4) to more than 2000% of normal (aav-1, -2, and ... | 2003 | 12791653 |
| [identification of bone marrow stromal cells and expression of tyrosine hydroxylase gene in them]. | the study is to establish the method of isolation and identification of bone marrow stromal cells and to investigate the ability of bone marrow stromal cells to accept and express th gene. cells were isolated by a density gradient (lymphocytes separation) and identified by brdu labeling and fluorescence-activated cell sorting (facs) technology using cd11b, cd45 and cd90 antibodies. th and lacz gene were transfected to rbmscs with an adeno-associated virus vector. the results showed that most tig ... | 2003 | 12796814 |
| second-strand genome conversion of adeno-associated virus type 2 (aav-2) and aav-5 is not rate limiting following apical infection of polarized human airway epithelia. | recombinant adeno-associated virus type 5 (raav-5) is known to efficiently transduce airway epithelia via apical infection. in contrast, raav-2 has been shown to be inherently ineffective at transducing airway epithelia from the apical surface. however, tripeptide proteasome inhibitors (such as llnl) can dramatically enhance raav-2 transduction from the apical surface of human polarized airway epithelia by modulating the intracellular trafficking and processing of the virus. to further investiga ... | 2003 | 12805434 |
| platelet-derived growth factor-producing cells immortalized from rat mesencephalon with sv40 large t antigen transduced by an aav vector. | adeno-associated virus (aav) can infect a wide variety of mammalian cell types and is capable of infecting both dividing and non-dividing cell populations. here we report the construction of a recombinant aav vector which expresses the sv40 large t protein (aav-t) and the use of this vector to immortalize primary cells from embryonic rat mesencephalon. | 2003 | 12808197 |
| [construction of recombinant adeno-associated virus carrying hepatitis b surface antigen gene and preliminary study of the gene expression and function]. | to construct recombinant adeno-associated virus (raav) carrying hepatitis b surface antigen (hbsag) gene and study the function of the expressed hbsag. | 2003 | 12810373 |
| [development of gene therapy for hematopoietic stem cell using viral vectors]. | hematopoietic stem cells (hsc) are attractive targets for gene therapy of inherited and acquired disorders in hematopoietic system in that they possess the properties of self-renewal, proliferation, and multi-lineage differentiation. for successful gene therapy, the viral vector-mediated gene addition strategy has two essential prerequisites: 1) the efficient transfer of therapeutic gene into hsc; 2) the long-term and stable expression of the transgene at therapeutic levels. the oncoretrovirus-d ... | 2003 | 12812066 |
| third-generation lentivirus vectors efficiently transduce and phenotypically modify vascular cells: implications for gene therapy. | grafting of saphenous vein (sv) conduits into the arterial circulation triggers a number of adaptive pathological changes characterized by progressive medial thickening, neointima formation and accelerated atheroma. previous studies have shown that modification of vein graft biology is possible by adenovirus (ad)-mediated gene transfer, although gene expression is transient. advancement of vascular gene therapy to the clinic is compromised by the lack of safe and efficient vector systems that pr ... | 2003 | 12818564 |
| anterograde delivery of brain-derived neurotrophic factor to striatum via nigral transduction of recombinant adeno-associated virus increases neuronal death but promotes neurogenic response following stroke. | to explore the role of brain-derived neurotrophic factor for survival and generation of striatal neurons after stroke, recombinant adeno-associated viral vectors carrying brain-derived neurotrophic factor or green fluorescent protein genes were injected into right rat substantia nigra 4-5 weeks prior to 30 min ipsilateral of middle cerebral artery occlusion. the brain-derived neurotrophic factor-recombinant adeno-associated viral transduction markedly increased the production of brain-derived ne ... | 2003 | 12823474 |
| a biochemical characterization of the adeno-associated virus rep40 helicase. | the human adeno-associated virus (aav) has generated much enthusiasm as a transfer vector for human gene therapy. although clinical gene therapy trials have been initiated using aav vectors, much remains to be learned regarding the basic mechanisms of virus replication, gene expression, and virion assembly. aav encodes four nonstructural, or replication (rep), proteins. the rep78 and rep68 proteins regulate viral dna replication, chromosomal integration, and gene expression. the rep52 and rep40 ... | 2003 | 12824181 |
| hiv-1 p55gag encoded in the lysosome-associated membrane protein-1 as a dna plasmid vaccine chimera is highly expressed, traffics to the major histocompatibility class ii compartment, and elicits enhanced immune responses. | several genetic vaccines encoding antigen chimeras containing the lysosome-associated membrane protein (lamp) translocon, transmembrane, and cytoplasmic domain sequences have elicited strong mouse antigen-specific immune responses. the increased immune response is attributed to trafficking of the antigen chimera to the major histocompatibility class ii (mhc ii) compartment where lamp is colocalized with mhc ii. in this report, we describe a new form of an hiv-1 p55gag dna vaccine, with the gag s ... | 2003 | 12824194 |
| practical considerations of recombinant adeno-associated virus-mediated gene transfer for treatment of retinal degenerations. | photoreceptor (pr) and retinal pigment epithelium (rpe) are the principal cell targets in retinal gene therapy. recombinant adeno-associated virus (raav) has emerged as a very promising vector for gene therapy in hereditary retinal diseases. gene transfer at different stages of the disease is a practical consideration for future clinical application. | 2003 | 12825197 |
| pathways of removal of free dna vector ends in normal and dna-pkcs-deficient scid mouse hepatocytes transduced with raav vectors. | elucidation of the mechanisms of transformation of single-stranded (ss) recombinant adeno-associated virus (raav) vector genomes into a variety of stable double-stranded (ds) forms is key to a complete understanding of raav vector transduction in vivo. ds monomer genome formation and cellular ds dna break (dsb) repair pathways that remove free vector ends toxic to cells, presumably play a central role in this process. by delivering raav and naked ds linear dna vectors into livers of dna-dependen ... | 2003 | 12828858 |
| delivery of adeno-associated virus vectors to the fetal retina: impact of viral capsid proteins on retinal neuronal progenitor transduction. | the development of fetal ocular gene transfer may be useful as a therapeutic tool for the prevention of retinal genetic disorders with congenital or early clinical manifestations. in this study we explored the neural progenitor transduction patterns of adeno-associated virus (aav) vectors following delivery to the developing retina. recombinant vectors with the same genome carrying the enhanced green fluorescent protein (egfp) transgene packaged in capsids of differing serotypes (serotypes 1, 2, ... | 2003 | 12829835 |
| receptor targeting of adeno-associated virus vectors. | adeno-associated virus (aav) is a promising vector for human somatic gene therapy. however, its broad host range is a disadvantage for in vivo gene therapy, because it does not allow the selective tissue- or organ-restricted transduction required to enhance the safety and efficiency of the gene transfer. therefore, increasing efforts are being made to target aav-2-based vectors to specific receptors. the studies summarized in this review show that it is possible to target aav-2 to a specific cel ... | 2003 | 12833123 |
| leptin-induced leptin resistant rats exhibit enhanced responses to the melanocortin agonist mt ii. | the purpose of this study was to determine if leptin could induce a leptin resistance in young rats and if leptin-induced leptin resistant rats are responsive to the melanocortin agonist, melanotan ii (mt ii). recombinant adeno-associated virus encoding rat leptin cdna (raav-leptin) or control viral vector were administered into young, lean rats for 300 days, and food consumption, body weight, oxygen consumption, serum leptin, and leptin signal transduction were measured. in the raav-leptin rats ... | 2003 | 12842127 |
| comparison of gene expression after intraperitoneal delivery of aav2 or aav5 in utero. | correction of diseases may be achieved by delivery of genes to stem cells and developing organ systems. our previous studies demonstrated life-long expression after in utero injection of adeno-associated virus (aav) serotype 2 in mice. in the present studies, we compared levels of expression using the elongation factor 1alpha (ef1alpha) or the cmv promoter in aav2 and aav5 linked to luciferase via intraperitoneal injection in day 15 fetuses in utero. an additional aav construct also contained th ... | 2003 | 12842432 |
| in vitro selection of viral vectors with modified tropism: the adeno-associated virus display. | improving the efficiency and specificity of gene vectors is critical for the success of gene therapy. in an effort to generate viral mutants with controlled tropism we produced a library of adeno-associated virus (aav) clones with randomly modified capsids and used it for the selection of receptor-targeting mutants. after several rounds of selection on different cell lines that were resistant to infection by wild-type (wt) aav, infectious mutants were harvested at high titers. these mutants tran ... | 2003 | 12842438 |
| adeno-associated virus mediated gene delivery into coronary microvessels of chronically instrumented dogs. | the objective of this study was to assess the potential of adeno-associated virus (aav)-mediated gene delivery into coronary microvessels in vivo in a large animal. ten mongrel dogs were chronically instrumented and allowed to recover for 10 days. dogs were reanesthetized, and the aorta was constricted by a hydraulic occluder, whereby left ventricular (lv) pressure increased by 30% and left circumflex coronary artery blood flow by 50%. recombinant aav (serotype 2, cmv enhancer/chicken beta-actin ... | 2003 | 12844500 |
| modeling cns neurodegeneration by overexpression of disease-causing proteins using viral vectors. | defective handling of proteins is a central feature of major neurodegenerative diseases. the discovery that neuronal dysfunction or degeneration can be caused by mutations in single cellular proteins has given new opportunities to model the underlying disease processes by genetic modification of cells in vitro or by generation of transgenic animals carrying the disease-causing gene. recent developments in recombinant viral-vector technology have opened up an interesting alternative possibility, ... | 2003 | 12850435 |
| adeno-associated virus mediated lacz gene transfect to cultured human iris pigment epithelium cells. | to study the feasibility of adeno-associated virus mediated gene transfection to cultured human iris pigment epithelium (ipe) cells in vitro. | 2003 | 12852088 |
| construction of a recombinant vector based on aav carrying human endothelial nitric-oxide synthase gene. | to construct an aav based vector carrying human endothelial nitric-oxide synthase (enos) cdna and study its expression in vitro for future gene therapy. | 2003 | 12852827 |
| testing recombinant adeno-associated virus-gene loading of dendritic cells for generating potent cytotoxic t lymphocytes against a prototype self-antigen, multiple myeloma hm1.24. | recent studies demonstrate that recombinant adeno-associated virus (raav)-based antigen loading of dendritic cells (dcs) generates significant and rapid (one stimulation per week) cytotoxic t-lymphocyte (ctl) responses in vitro against viral antigens. as a more extensive analysis of the raav system, we have used a self-antigen, hm1.24, expressed in multiple myeloma (mm). again, with one stimulation, significant major histocompatibility complex (mhc) class 1-restricted, anti-hm1.24-specific ctl k ... | 2003 | 12855576 |
| gene treatment of cerebral stroke by raav vector delivering il-1ra in a rat model. | in this study, we injected recombinant adeno-associated virus (raav) vectors expressing the interleukin-1 receptor antagonist (raav-il-1ra) into the cortex of rats experiencing transient cerebral ischemia. an accumulation of il-1ra in cortical tissues of raav-il-1ra-injected animals was confirmed by elisa. triphenyltetrazolium chloride (ttc) staining of viable brain tissue revealed that the raav-delivered il-1ra gene could rescue the brain tissues from ischemia-induced injury. cortical tissues t ... | 2003 | 12858036 |
| attenuation of seizures and neuronal death by adeno-associated virus vector galanin expression and secretion. | seizure disorders present an attractive gene therapy target, particularly because viral vectors such as adeno-associated virus (aav) and lentivirus can stably transduce neurons. when we targeted the n-methyl-d-aspartic acid (nmda) excitatory amino acid receptor with an aav-delivered antisense oligonucleotide, however, the promoter determined whether focal seizure sensitivity was significantly attenuated or facilitated. one potential means to circumvent this liability would be to express an inhib ... | 2003 | 12858168 |
| enhancement of expression of vascular endothelial growth factor after adeno-associated virus gene transfer is associated with improvement of brain ischemia injury in the gerbil. | angiogenesis induced by growth factors may represent a rational therapy for patients with stroke. vascular endothelial growth factor (vegf) plays a pivotal role in angiogenesis and vegf expression is enhanced in the post-ischemic brain. vegf induced by brain hypoxia can lead to the growth of new vessels and may represent a natural protective mechanism improving survival after stroke. in the light of these findings we investigated changes of vegf expression in different brain regions after intrac ... | 2003 | 12860452 |
| functional change of human peripheral blood monocyte-derived dendritic cells after recombinant adeno-associated virus type 2-mediated hbsag gene infection. | to observe the changes in the functions of human peripheral blood monocyte-derived dendritic cells (dcs) after hepatitis b virus surface antigen (hbsag) gene infection mediated by recombinant adeno-associated virus type 2 (raav). | 2003 | 12865224 |
| positive and negative effects of adeno-associated virus rep on aavs1-targeted integration. | adeno-associated virus type 2 integrates preferentially into the aavs1 locus on chromosome 19 of the human genome. it was reported previously that transfection with two plasmids, one for rep and the other carrying a transgene flanked by inverted terminal repeats (itrs), enables preferential integration of the latter into aavs1. aiming at increasing the frequency of aavs1-specific integration, the rep- to transgene-plasmid ratio necessary to achieve a higher frequency of site-specific integration ... | 2003 | 12867644 |
| [construction of human papilloma virus type 18 e6e7 genes in adeno-associated virus expression vector and checking its activity for malignant transformation]. | to construct human papillomavirus type 18 (hpv18 e6e7) adeno-associated virus (aav) for studying the role of hpv e6e7 in the development of human cancer. | 2003 | 12870008 |
| from virus evolution to vector revolution: use of naturally occurring serotypes of adeno-associated virus (aav) as novel vectors for human gene therapy. | gene transfer vectors based on the human adeno-associated virus serotype 2 (aav-2) have been developed and tested in pre-clinical studies for almost 20 years, and are currently being evaluated in clinical trials. so far, all these studies have provided evidence that aav-2 vectors possess many properties making them very attractive for therapeutic gene delivery to humans, such as a lack of pathogenicity or toxicity, and the ability to confer long-term gene expression. however, there is concern th ... | 2003 | 12871018 |
| a single adeno-associated virus (aav)-murine factor viii vector partially corrects the hemophilia a phenotype. | a major obstacle for delivery of factor (f)viii using adeno-associated virus (aav) vectors is the large size of fviii cdna, which is well above the 5 kb packaging limit for aav. here we construct a < 5 kb fviii-aav vector using murine fviii cdna and a strong liver-specific albumin promoter. we assessed the efficacy of this vector using three different routes of administration, intraportal, intrasplenic and tail vein injection, in fviii knockout (fviii ko) mice. the peak level of fviii observed w ... | 2003 | 12871492 |
| shuttle pcr-based cloning of the infectious adeno-associated virus type 5 genome. | adeno-associated virus type 5 (aav5), which is distinct from the other serotypes of aav, has attracted considerable interest as a premier gene delivery vector. as do the other serotypes, aav5 contains its 4.7 kb-sized, single-stranded genome flanked with inverted terminal repeats (itrs) in a hairpin conformation, which serves frequently as pause and arrest sites for dna polymerases during pcr. to amplify the full-length of the aav5 genome in single step, we established a shuttled, long and accur ... | 2003 | 12880922 |
| central pro-opiomelanocortin gene delivery results in hypophagia, reduced visceral adiposity, and improved insulin sensitivity in genetically obese zucker rats. | zucker (fa/fa) rats with defective leptin receptors are obese, hyperphagic, and hyperinsulinemic. for testing whether chronic activation of the central melanocortin pathway can bypass the defective leptin signaling and normalize altered energy homeostasis in these rats, recombinant adeno-associated virus encoding pro-opiomelanocortin (raav-pomc) or control vector was delivered bilaterally into the basal hypothalamus with coordinates targeting the arcuate nucleus. thirty-eight days after pomc gen ... | 2003 | 12882910 |
| stable raav-mediated transduction of rod and cone photoreceptors in the canine retina. | recombinant adeno-associated virus (raav) vectors are attractive candidates for the treatment of inherited and acquired retinal disease. although raav vectors are well characterized in rodent models, a prerequisite to their clinical application in human patients is the thorough evaluation of their efficacy and safety in intermediate animal models. in this study, we describe raav-2-mediated expression of gfp reporter gene in retinal cells following local vector delivery in dogs. subretinal delive ... | 2003 | 12883530 |
| gene therapy for new bone formation using adeno-associated viral bone morphogenetic protein-2 vectors. | previous reports have suggested that bone morphogenetic protein (bmp) gene therapy could be applied for in vivo bone regeneration. however, these studies were conducted either using immunodeficient animals because of immunogenicity of adenovirus vectors, or using ex vivo gene transfer technique, which is much more difficult to handle. adeno-associated virus (aav) is a replication-defective virus without any association with immunogenicity and human disease. this study was conducted to investigat ... | 2003 | 12883531 |
| phase i trial of intranasal and endobronchial administration of a recombinant adeno-associated virus serotype 2 (raav2)-cftr vector in adult cystic fibrosis patients: a two-part clinical study. | recombinant adeno-associated serotype 2-based vectors (raav2) possess a number of theoretical advantages for cystic fibrosis (cf) gene therapy because they elicit little or no inflammatory response and generally result in stable expression. raav2 vectors expressing the cystic fibrosis transmembrane conductance regulator (cftr) gene have previously been shown to mediate stable correction of the cf defect in cf bronchial epithelial cells and stable expression of cftr in rabbit and nonhuman primate ... | 2003 | 12885347 |
| identification of an insulator in aavs1, a preferred region for integration of adeno-associated virus dna. | in latent adeno-associated virus (aav) infection, the viral genome is integrated preferentially into the human chromosome 19 q arm at a specific region designated aavs1, which has an open chromatin conformation as indicated by the presence of a dnase i-hypersensitive site (dhs-s1). we examined whether an insulator, which defines the domain of gene expression by directionally blocking the action of enhancers and by preventing the spread of heterochomatin, is present near the dhs-s1 in the middle ... | 2003 | 12885916 |
| cd4+cd25+ regulatory t cells inhibit immune-mediated transgene rejection. | like cellular transplantation, gene therapy is often limited by immune rejection of the newly expressed antigen. in a model of gene transfer in muscle, delivery of the influenza hemagglutinin (ha) membrane protein by adeno-associated virus (aav) is impaired by a strong immune response that leads to a rapid rejection of the transduced fibers. we show here that injection of ha-specific cd4+cd25+ t cells from t-cell receptor (tcr)-transgenic animals, concomitant with gene transfer, down-regulates t ... | 2003 | 12893754 |
| random peptide libraries displayed on adeno-associated virus to select for targeted gene therapy vectors. | characterizing the molecular diversity of the cell surface is critical for targeting gene therapy. cell type-specific binding ligands can be used to target gene therapy vectors. however, targeting systems in which optimum eukaryotic vectors can be selected on the cells of interest are not available. here, we introduce and validate a random adeno-associated virus (aav) peptide library in which each virus particle displays a random peptide at the capsid surface. this library was generated in a thr ... | 2003 | 12897791 |
| recombinant aav serotype 1 transduction efficiency and tropism in the murine brain. | recombinant adeno-associated virus serotype 2 (raav2) vectors have shown promise as therapeutic agents for neurologic disorders. however, intracerebral administration of this vector leads to preferential transduction of neurons and a restricted region of transgene expression. the recently developed raav vectors based upon nonserotype 2 viruses have the potential to overcome these limitations. therefore, we directly compared a raav type 1 to a type 2 vector in the murine brain. the vectors were e ... | 2003 | 12900769 |
| [quality control of recombinant adeno-associated virus type 2/human blood coagulation factor ix]. | to establish quality control requirements and methods for recombinant adeno-associated virus(raav) type 2/human blood coagulation factor ix (raav-2/hfix). | 2003 | 14730919 |
| [gene therapy using aav (adeno-associated virus) vectors]. | 2003 | 15080081 | |
| intracavernosal vascular endothelial growth factor (vegf) injection and adeno-associated virus-mediated vegf gene therapy prevent and reverse venogenic erectile dysfunction in rats. | penile veno-occlusive dysfunction (venogenic erectile dysfunction) is a common cause of erectile dysfunction (ed). we investigated whether vascular endothelial growth factor (vegf) can be used to prevent and reverse venogenic ed in a rat model. pharmacological cavernosometry was developed and validated using adult male rats with either arteriogenic or venogenic ed. castrated animals were treated with intracavernous vegf as either a recombinant protein (c+vegf) or adeno-associated virus (aav)-med ... | 2003 | 12605238 |
| adeno-associated virus-mediated il-10 gene therapy inhibits diabetes recurrence in syngeneic islet cell transplantation of nod mice. | islet transplantation represents a potential cure for type 1 diabetes, yet persistent autoimmune and allogeneic immunities currently limit its clinical efficacy. for alleviating the autoimmune destruction of transplanted islets, newly diagnosed nod mice were provided a single intramuscular injection of recombinant adeno-associated viral vector encoding murine il-10 (raav-il-10) 4 weeks before renal capsule delivery of 650 syngeneic islets. a dose-dependent protection of islet grafts was observed ... | 2003 | 12606512 |
| enhanced recombinant adeno-associated virus-mediated vascular endothelial growth factor expression in the adult mouse retina: a potential model for diabetic retinopathy. | diabetic retinopathy, one of the most serious complications of long-term diabetes, could clinically be divided into two stages: 1) background retinopathy that does not cause visual impairment and 2) proliferative retinopathy, which is a potentially blinding condition. this study aims to investigate the correlation between enhancement of vascular endothelial growth factor (vegf) expression and neovascular changes. a binary recombinant adeno-associated virus construct producing green fluorescent p ... | 2003 | 12606531 |
| genetic fate of recombinant adeno-associated virus vector genomes in muscle. | recombinant adeno-associated virus (raav) vectors are promising human gene transfer vectors, because they mediate long-term gene expression in vivo. the vector dna form responsible for sustained gene expression has not been clearly defined, but it has been presumed that the vector integrates to some degree and persists in this manner. using two independent methods, we were unable to identify raav integrants in mouse muscle. in the first approach, we were unable to recover host cell-vector dna ju ... | 2003 | 12610125 |
| production, purification and preliminary x-ray crystallographic studies of adeno-associated virus serotype 4. | adeno-associated virus (aav) serotypes 1 to 5 are currently under development as clinical gene delivery vectors for the treatment of human diseases. however, the ubiquitous nature of their cell surface receptors, heparin sulfate (aav2 and 3) and sialic acids (aav4 and 5), can preclude specific tissue targeting in vivo. structural studies of aav4 were initiated to characterize its capsid surface for re-targeting manipulations. crystals obtained diffracted synchrotron radiation to 3.2 a resolution ... | 2003 | 12620791 |
| neuroglobin protects the brain from experimental stroke in vivo. | neuroglobin (ngb) is an o(2)-binding protein localized to cerebral neurons of vertebrates, including humans. its physiological role is unknown but, like hemoglobin, myoglobin, and cytoglobin/histoglobin, it may transport o(2), detoxify reactive oxygen species, or serve as a hypoxia sensor. we reported recently that hypoxia stimulates transcriptional activation of ngb in cultured cortical neurons and that antisense inhibition of ngb expression increases hypoxic neuronal injury, whereas overexpres ... | 2003 | 12621155 |
| long-term correction of globotriaosylceramide storage in fabry mice by recombinant adeno-associated virus-mediated gene transfer. | fabry disease is an x-linked recessive inborn metabolic disorder characterized by systemic and vascular accumulation of globotriaosylceramide (gb(3)) caused by a deficiency of the lysosomal enzyme alpha-galactosidase a (alpha-gal a). the condition is associated with an increased morbidity and mortality due to renal failure, cardiac disease, and early onset of stroke. hemizygous males are primarily affected clinically with variable expression in heterozygous females. gene-therapy trials have been ... | 2003 | 12624185 |
| distribution of fluorescence following injection of recombinant adeno-associated virus encoding green fluorescent protein into the paraventricular nucleus. | we have used recombinant type 2 adeno-associated virus to deliver the gene encoding green fluorescent protein into the central nervous system of adult rats. gene expression, determined by fluorescent microscopy, was observed not only at the site of injection but also in axons following known neuroanatomical pathways. we have demonstrated a spread of enhanced green fluorescent protein from the paraventricular nucleus of the hypothalamus into the median eminence and neurohypophysis. cell bodies co ... | 2003 | 12624531 |
| the effect of vascular endothelial growth factor and adeno-associated virus mediated brain derived neurotrophic factor on neurogenic and vasculogenic erectile dysfunction induced by hyperlipidemia. | we examined neurogenic and vasculogenic erectile dysfunction associated with hypercholesterolemia and evaluated vascular endothelial growth factor (vegf) and adeno-associated virus (aav) mediated, brain derived neurotrophic factor (bdnf) for potential treatment. | 2003 | 12629419 |
| gene transfer into human keloid tissue with adeno-associated virus vector. | background gene transfer is a new territory for clinicians. intractable disorders might be approached in such a way. adeno-associated virus (aav) vector has been transfected successfully into a variety of tissues including skin. we evaluated the ability of this vector to transfer and cause expression of the reporter gene in human keloid tissue. methods human keloid specimens were injected with an aav vector encoding beta-galactosidase and incubated for 4 weeks after injection. the presence of mr ... | 2003 | 12634540 |
| efficient adeno-associated virus-mediated gene expression in human placenta-derived mesenchymal cells. | mesenchymal cells from various sources are pluripotent and are attractive sources for cell transplantation. in this study, we analyzed recombinant adeno-associated virus (raav)-mediated gene expression in human placenta-derived mesenchymal cells (hpdmcs), which reside in placental villi. after transduction of av-cag-egfp, a raav expressing enhanced green fluorescence protein (egfp), hpdmcs showed much higher level of egfp expression than human umbilical vein endothelial cells or rat aortic smoot ... | 2003 | 12636261 |
| effect of adeno-associated virus-specific immunoglobulin g in human amniotic fluid on gene transfer. | intra-amniotic administration of adeno-associated virus (aav) vector may be an effective way to deliver gene therapy for treatment of congenital pulmonary and intestinal disorders. in an effort to understand potential barriers to intra-amniotic gene therapy better, we determined whether human amniotic fluid (af) could act as an inhibitor of aav2-mediated gene transfer. af samples were obtained from 21 different human pregnancies during routine amniocentesis at 16-20 weeks of gestation. an immort ... | 2003 | 12659677 |
| recombinant adeno-associated virus vectors efficiently and persistently transduce chondrocytes in normal and osteoarthritic human articular cartilage. | successful gene transfer into articular cartilage is a prerequisite for gene therapy of articular joint disorders. in the present study we tested the hypothesis that recombinant adeno-associated virus (raav) vectors are capable of effecting gene transfer in isolated articular chondrocytes in vitro, articular cartilage tissue in vitro, and sites of articular damage in vivo. using an raav vector carrying the escherichia coli beta-galactosidase gene (lacz) under the control of the cytomegalovirus ( ... | 2003 | 12659680 |
| development of genetically engineered human intestinal cells for regulated insulin secretion using raav-mediated gene transfer. | cell-based therapies for treating insulin-dependent diabetes (idd) can provide a more physiologic regulation of blood glucose levels in a less invasive fashion than daily insulin injections. promising cells include intestinal enteroendocrine cells genetically engineered to secrete insulin in response to physiologic stimuli; responsiveness occurs at the exocytosis level to regulate the acute release of recombinant insulin. in this work, we established a human cellular model to demonstrate that me ... | 2003 | 12659868 |
| pka/prkx activity is a modulator of aav/adenovirus interaction. | interference between viruses occurs when infection by one virus results in the inhibition of replication of another virus. adeno-associated virus (aav2) is a human parvovirus with the unique characteristics of a dependence upon a helper virus for a productive infection and the ability to interfere with the replication of the helper virus. previously, we demonstrated that aav2 rep78 and rep52 interact and inhibit camp-dependent protein kinase a (pka) and its novel homolog prkx. we hypothesized th ... | 2003 | 12660177 |