| current status of viral gene therapy for brain tumours. | malignant glial tumours represent the majority of primary brain tumours. despite the use of many adjunctive treatment strategies in addition to surgery, the prospect of cure or even long-term survival is poor. in the last decade, there has been an explosion of interest in the development of delivery systems that will allow the expression of exogenous genes in the cns. for the most part, these systems are based upon modified viruses. to date, the greatest experience has been with retroviruses, he ... | 2000 | 11060704 |
| critical aspects of viral vectors for gene transfer into the kidney. | viral vectors have been used in vitro and in vivo for more than a decade, with some significant results in specific situations, e.g., when recombinant adeno-associated virus is used for the long-term transduction of skeletal muscle in coagulation factor ix-deficient patients. however, the kidney has been quite difficult to transduce with any viral vector currently available. when viral transduction occurs, it is often heterogeneous, transient, and eventually associated with immune and toxic side ... | 2000 | 11065348 |
| adeno-associated virus vectors for gene therapy: more pros than cons? | gene therapy vectors based on the adeno-associated virus (aav) are being developed for a widening variety of therapeutic applications. enthusiasm for aav is due, not only to the relative safety of these vectors, but also to advances in understanding of the unique biology of this virus. this review examines a number of long-standing concerns regarding the utility of aav for gene transfer in light of many new insights into the biology, immunology and production of aav. | 2000 | 11074369 |
| in vivo transduction of cerebellar purkinje cells using adeno-associated virus vectors. | we investigated whether adenovirus or adeno-associated virus vectors can transduce cerebellar purkinje cells (pcs) in vivo. mice were injected in the deep cerebellar nuclei (dcn) with lacz-transducing adenovirus (ad.rsv-betagal) or a recombinant aav serotype 2 (raav2) vector (vtr-cmvbeta) mixed with wild-type adenovirus type 5 (ad5). one week later, ad.rsv-betagal transduced cells were found throughout the cerebellar white matter in a dose-dependent manner, but few transduced pcs were evident. i ... | 2000 | 11082318 |
| inhibition of recombinant adeno-associated virus (raav) transduction by bronchial secretions from cystic fibrosis patients. | the conducting airways are the primary target for gene transfer in cystic fibrosis (cf), yet the inflammation associated with cf lung disease could potentially pose a significant barrier to gene transfer vectors, such as recombinant adeno-associated virus (raav). in order to investigate this possibility, aliquots of bronchoalveolar lavage (bal) fluid from eight individuals with cf were tested for their in vitro inhibitory effects on raav transduction, along with bal from non-cf individuals. whil ... | 2000 | 11083501 |
| recombinant adeno-associated virus vector expressing glial cell line-derived neurotrophic factor reduces ischemia-induced damage. | to explore the potential of using the recombinant adeno-associated viral (raav) vector, expressing glial cell line-derived neurotrophic factor (gdnf) as the gene therapy for stroke, we injected raav vectors expressing gdnf (raav-gdnf) into the cortex of rats which had been experiencing transient bilateral common carotid artery ligation and right middle cerebral artery ligation for 90 min. gdnf levels in cortical tissues of raav-gdnf-injected animals were significantly higher than in the control ... | 2000 | 11085892 |
| the adenovirus e4 orf6 and e1b 55 kda proteins cooperate in a p53-independent manner to enhance transduction by recombinant adeno-associated virus vectors. | the observation that exposure of target cells to genotoxic stress or adenovirus infection enhances recombinant adeno-associated virus (raav) transduction is an important lead towards defining the raav transduction mechanism, and has significant implications for the exploitation of raav in gene therapy applications. the adenovirus-mediated enhancement of raav transduction has been mapped to the e4 orf6 gene, and expression of e4 orf6 alone has been considered necessary and sufficient to mediate t ... | 2000 | 11086129 |
| glucose-responsive gene delivery in pancreatic islet cells via recombinant adeno-associated viral vectors. | recent progress in genetic engineering presents the possibility of providing physiologically regulated glucose metabolism in individuals with diabetes. the objective of this study is to explore the feasibility of obtaining glucose dependent gene expression in the pancreatic beta-cell lines via recombinant adeno-associated virus type 2 (raav) mediated gene transfer. | 2000 | 11087036 |
| high-titer, wild-type free recombinant adeno-associated virus vector production using intron-containing helper plasmids. | recombinant adeno-associated virus (raav) is capable of directing long-term, high-level transgene expression without destructive cell-mediated immune responses. however, traditional packaging methods for raav vectors are generally inefficient and contaminated with replication-competent aav (rcaav) particles. although wild-type aav is not associated with any known human diseases, contaminating rcaav particles may affect raav gene expression and are an uncontrolled variable in many aav gene transf ... | 2000 | 11090141 |
| efficient replication of adeno-associated virus type 2 vectors: a cis-acting element outside of the terminal repeats and a minimal size. | recombinant adeno-associated virus type 2 (aav2) can be produced in adenovirus-infected cells by cotransfecting a plasmid containing the recombinant aav2 genome, which is generally comprised of the viral terminal repeats flanking a transgene, together with a second plasmid expressing the aav2 rep and cap genes. however, recombinant viruses generally replicate inefficiently, often producing 100-fold fewer virus particles per cell than can be obtained after transfection with a plasmid containing a ... | 2000 | 11090148 |
| adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model. | duchenne muscular dystrophy (dmd) is the most common and lethal genetic muscle disorder, caused by recessive mutations in the dystrophin gene. one of every 3,500 males suffers from dmd, yet no treatment is currently available. genetic therapeutic approaches, using primarily myoblast transplantation and adenovirus-mediated gene transfer, have met with limited success. adeno-associated virus (aav) vectors, although proven superior for muscle gene transfer, are too small (5 kb) to package the 14-kb ... | 2000 | 11095710 |
| adeno-associated virus production of soluble tumor necrosis factor receptor neutralizes tumor necrosis factor alpha and reduces arthritis. | the major limitation of adenovirus is its association with induction of an inflammatory response and relatively short-term production of the gene therapy transgene product. adeno-associated virus (aav) is a 4.68-kb single-strand dna virus that contains itrs for viral replication and a packaging signal, and also has been engineered to contain therapeutic genes up to 5 kb in length. transduction of recombinant aav (raav) results in low inflammatory response and long-term expression. we have cloned ... | 2000 | 11096446 |
| long-term real-time monitoring of adeno-associated virus-mediated gene expression in the rat retina. | previous studies have demonstrated that adeno-associated virus (aav) efficiently transduced retinal pigmented epithelial (rpe) cells. the goal of this study was to further evaluate and characterize transgene expression within the rpe cells over time in vivo. | 2000 | 11097287 |
| remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue. | a cure for diabetes has long been sought using several different approaches, including islet transplantation, regeneration of beta cells and insulin gene therapy. however, permanent remission of type 1 diabetes has not yet been satisfactorily achieved. the development of type 1 diabetes results from the almost total destruction of insulin-producing pancreatic beta cells by autoimmune responses specific to beta cells. standard insulin therapy may not maintain blood glucose concentrations within t ... | 2000 | 11100731 |
| successful interference with cellular immune responses to immunogenic proteins encoded by recombinant viral vectors. | vectors derived from the adeno-associated virus (aav) have been successfully used for the long-term expression of therapeutic genes in animal models and patients. one of the major advantages of these vectors is the absence of deleterious immune responses following gene transfer. however, aav vectors, when used in vaccination studies, can result in efficient humoral and cellular responses against the transgene product. it is therefore important to understand the factors which influence the establ ... | 2001 | 11119597 |
| characterization of adenovirus-induced inverted terminal repeat-independent amplification of integrated adeno-associated virus rep-cap sequences. | stable packaging cell lines expressing the rep and cap genes for recombinant adeno-associated virus type 2 (raav-2) assembly constitute an attractive alternative to transient transfection protocols. we recently characterized a stable hela rep-cap cell clone (herc32) and demonstrated that upon vector transfection and adenovirus infection, efficient raav assembly correlated with a 100-fold amplification of the integrated rep-cap sequence with the inverted terminal repeats (itrs) deleted. we now re ... | 2001 | 11119606 |
| towards a neuroprotective gene therapy for parkinson's disease: use of adenovirus, aav and lentivirus vectors for gene transfer of gdnf to the nigrostriatal system in the rat parkinson model. | during the last few years, recombinant viral vectors derived from adenovirus (ad), adeno-associated virus (aav) or lentivirus (lv) have been developed into highly effective vehicles for gene transfer to the adult central nervous system. in recent experiments, in the rat model of parkinson's disease, all three vector systems have been shown to be effective for long-term delivery of glial cell line-derived neurotrophic factor (gdnf) at biologically relevant levels in the nigrostriatal system. inje ... | 2000 | 11119690 |
| perfluorochemical liquid enhances adeno-associated virus-mediated transgene expression in lungs. | use of adeno-associated virus (aav) vectors for lung gene therapy is limited, in part, by low levels of aav-mediated transgene expression in lungs. generally, less than 1% of total airway and alveolar epithelial cells express transgene activity following vector administration. a means of improving aav vector delivery could potentially enhance aav-mediated gene expression in lungs. we have previously demonstrated that use of perfluorochemical (pfc) liquids improved overall levels of adenovirus ve ... | 2000 | 11124064 |
| a quantitative nonimmunogenic transgene product for evaluating vectors in nonhuman primates. | the success of gene therapy depends on safe, effective vectors to transfer genetic information. we have developed a means to quantitatively assess efficacy of gene transfer vectors by using a biologically inert, secreted reporter molecule, the beta chain of chorionic gonadotropin (beta-cg). using an isogenic beta chain subunit of cg in a recombinant adeno-associated virus (raav) vector, overall gene transfer of rhesus macaque muscle is demonstrated over time by measuring the serum concentration ... | 2000 | 11124068 |
| adeno-associated virus-mediated delivery of il-4 prevents collagen-induced arthritis. | immunomodulation of autoimmune inflammatory diseases like rheumatoid arthritis can be achieved by anti-inflammatory t2 cytokines such as interleukin (il)-4 administered by gene therapy. in this study we investigated the efficiency of adeno-associated viruses (aav) vectors in collagen-induced arthritis (cia). after injection of aav-lacz in the tarsus area of mice, the expression of the transgene was localized in the deep muscles cells near the bone. lacz expression was found in liver, heart and l ... | 2000 | 11127581 |
| recombinant adeno-associated virus vectors efficiently transduce foreign gene into bovine aortic endothelial cells: comparison with adenovirus vectors. | because the features and kinetics of adeno-associated virus (aav)-mediated gene transfer to endothelial cells (ec) are yet to be ultimately determined, we tested variables pertinent to the efficiency of aav-mediated gene transfer to bovine aortic endothelial cells (baec). the variables with aav vectors were compared with the better characterized adenovirus (ad) vectors. there is a dose-response relationship between multiplicity of infection (moi) of aav or ad vectors and transduction efficiency ... | 2000 | 11128044 |
| gene therapy of parkinson's disease using adeno-associated virus (aav) vectors. | parkinson's disease (pd) is characterized by the progressive loss of the dopaminergic neurons in the substantia nigra and a severe decrease in dopamine in the striatum. a promising approach to the gene therapy of pd is intrastriatal expression of dopamine-synthesizing enzymes [tyrosine hydroxylase (th) and aromatic l-amino acid decarboxylase (aadc)]. the most appropriate gene-delivery vehicles for neurons are adeno-associated virus (aav) vectors, which are derived from non-pathogenic virus. ther ... | 2000 | 11128607 |
| adeno-associated virus in normal and myositis human skeletal muscle. | the normal tissue tropism of adeno-associated virus (aav) is poorly defined, although the majority of humans test seropositive for this virus. eighty-five muscle biopsy specimens were tested for aav genomes; aav dna was identified in 17% of normal and 10% of duchenne muscular dystrophy muscle biopsy specimens, but in only 3% of peripheral blood samples. aav genomes were absent from all 37 muscle biopsy specimens from patients with myositis tested. muscle is a major target organ for aav, and infe ... | 2000 | 11134397 |
| gene therapy: recombinant adeno-associated virus vectors. | gene transfer using recombinant adeno-associated virus (raav) vectors shows great promise for human gene therapy. the broad host range, low level of immune response, and longevity of gene expression observed with these vectors in numerous disease paradigms has enabled the initiation of a number of clinical trials using this gene delivery system. this review presents an overview of the current developments in the field of aav-mediated gene delivery. such developments include the establishment of ... | 2001 | 11139798 |
| viral gene delivery. | experimental studies of viral gene delivery generally support the principle that virus-mediated gene transfer is indeed possible. however, the field of gene therapy has not yet been realised as a practicable clinical intervention. the delay in translation of laboratory work to clinical utility largely reflects the inability of gene delivery vectors to convey adequate genetic material to a desired location, with adequate durability and low enough toxicity to be effective. current studies of viral ... | 1999 | 11139845 |
| distribution of aav-tk following intracranial convection-enhanced delivery into rats. | adeno-associated virus (aav)-based vectors are being tested in animal models as viable treatments for glioma and neurodegenerative disease and could potentially be employed to target a variety of central nervous system disorders. the relationship between dose of injected vector and its resulting distribution in brain tissue has not been previously reported nor has the most efficient method of delivery been determined. here we report that convection-enhanced delivery (ced) of 2.5 x 10(8), 2.5 x 1 ... | 2000 | 11144956 |
| intracellular trafficking of adeno-associated virus vectors: routing to the late endosomal compartment and proteasome degradation. | the early steps of adeno-associated virus (aav) infection involve attachment to a variety of cell surface receptors (heparan sulfate, integrins, and fibroblast growth factor receptor 1) followed by clathrin-dependent or independent internalization. here we have studied the subsequent intracellular trafficking of aav particles from the endosomal compartment to the nucleus. human cell lines were transduced with a recombinant aav (raav) carrying a reporter gene (luciferase or green fluorescent prot ... | 2001 | 11160681 |
| efficient expression of the vascular endothelial growth factor gene in vitro and in vivo, using an adeno-associated virus vector. | vascular endothelial growth factor (vegf) has proven to be one of the most effective growth factors for therapeutic angiogenesis. the biological efficacy of the adeno-associated virus (aav) vector has recently been demonstrated in muscle tissues, including the heart. apart from these promising insights into vegf and the aav vector, studies on vegf gene transfer using the aav vector have been limited. here, we evaluate aav-mediated vegf gene transfer, both in vitro and in vivo, using the aav-mveg ... | 2001 | 11162134 |
| gene therapy for pulmonary diseases. | gene therapy for pulmonary disease has attracted a great deal of attention since the first report of successful gene delivery 10 years ago. potential indications for gene therapy include chronic illnesses such as cystic fibrosis and alpha(1)-antitrypsin deficiency, and acute illnesses such as acute transplant rejection and chemotherapy-induced lung injury. the key technological impediment to successful gene therapy is vector optimization. viral vectors, including adenovirus and adeno-associated ... | 2001 | 11171744 |
| long-term gene transfer to mouse fetuses with recombinant adenovirus and adeno-associated virus (aav) vectors. | we have developed a micro-injection technique to deliver recombinant adenovirus and aav to mouse fetuses at day 15 after conception. several routes of delivery, including injections to the amniotic fluid, the front limb, the placenta, the liver, and the retro-orbital venus plexus, were tested using an e1-deleted recombinant adenovirus (ad.cblacz) or a recombinant adeno-associated virus (aav.cmvlacz) carrying a beta-galactosidase (lacz) gene. injection of ad.cblacz into the amniotic cavity led to ... | 2000 | 11175309 |
| direct delivery of leptin to the hypothalamus using recombinant adeno-associated virus vectors results in increased therapeutic efficacy. | the hormone leptin has been shown to be an afferent signal in a negative-feedback loop regulating body weight, and consequently, the administration of the gene product for the treatment of obesity has recently attracted considerable attention. leptin is produced by adipocytes in response to increased trigyceride storage, and appears to affect body weight primarily through target cells in the hypothalamus. although plasma levels of leptin correlate positively with adipose tissue mass in normal hu ... | 2001 | 11175734 |
| selective repopulation of normal mouse liver by hepatocytes transduced in vivo with recombinant adeno-associated virus. | the use of recombinant adeno-associated virus (raav) as gene therapy vector for treating liver metabolic diseases is limited by its low transduction efficiency. we describe a strategy for achieving stable and efficient genetic reconstitution in liver after direct administration of raav and selective expansion of transduced cells. we have exploited the biology of apoptosis to develop a generic approach for selectively repopulating liver with vector-transduced hepatocytes. low-level, stable transd ... | 2001 | 11177541 |
| isolation of highly infectious and pure adeno-associated virus type 2 vectors with a single-step gravity-flow column. | one of the most promising gene transfer vectors in human clinical trials is aav2. the quality of the vector preparations is a key element in obtaining reliable and reproducible data in preclinical studies. however, established protocols either result in impure, low infectious virus (cscl2 gradient centrifugation) or demand a high level of manual and technical skills (cscl2 gradient centrifugation, iodixanol/heparin or hplc purification). in this study, we present an easy-to-do single-step column ... | 2001 | 11177544 |
| adeno-associated virus and lentivirus vectors mediate efficient and sustained transduction of cultured mouse and human dorsal root ganglia sensory neurons. | peripheral nervous system (pns) sensory neurons are directly involved in the pathophysiology of numerous inherited and acquired neurological conditions. therefore, efficient and stable gene delivery to these postmitotic cells has significant therapeutic potential. among contemporary vector systems capable of neuronal transduction, only those based on herpes simplex virus have been extensively evaluated in pns neurons. we therefore investigated the transduction performance of recombinant adeno-as ... | 2001 | 11177545 |
| muscle-specific promoters may be necessary for adeno-associated virus-mediated gene transfer in the treatment of muscular dystrophies. | recombinant adeno-associated virus (raav) vectors allow efficient gene transfer and expression in the muscle; therefore, raavs represent a potential gene therapy vector for muscular dystrophies. for further investigations, we used a mouse muscular dystrophy model (gsg(-/-) mice) gamma-sarcoglycan, a subunit of the dystrophin-glycoprotein complex, is missing. gsg(-/-) mice develop progressive dystrophy representative of a severe human phenotype disease. we previously showed high levels and stable ... | 2001 | 11177557 |
| direct gene delivery strategies for the treatment of rheumatoid arthritis. | gene therapy offers a novel and innovative approach to the delivery of therapeutic proteins to the joints of patients with arthritis. several viral vectors, including adenovirus, adeno-associated virus, retrovirus and herpes simplex virus, are capable of delivering exogenous cdnas to the synovial lining, enabling effective levels of intra-articular transgene expression following direct injection to the joint. the expression of certain gene products has proven to be sufficient to inhibit the prog ... | 2001 | 11182599 |
| [perspectives on postgenome medicine: hematological diseases]. | with advances in dna chip(dna microarray) technology, it has become possible to obtain genome-wide gene-expression profiling. this novel technology is now applied to the study of molecular pathogenesis, differential diagnosis, and prediction of prognosis in the field of hematological malignancies. importantly, the list of informative genes includes new markers of diseases, which will be utilized for further investigation. as for clinical gene therapy, it has been criticized for promising too muc ... | 2001 | 11197862 |
| principles of gene therapy: potential applications in the treatment of cerebral ischaemia. | in this review we explore gene therapy as a possible treatment for conditions causing cerebral ischaemia and briefly consider other neurological pathologies such as brain tumours. dna transfer may be achieved using retrovirus, herpes simplex virus, adenovirus, and adeno-associated virus vectors or liposomes. after cerebral ischaemia, these vectors are used to upregulate genes that increase survival and inhibit those that promote death in the injured cells. in contrast, in brain tumours gene ther ... | 2000 | 11198761 |
| scaleable chromatographic purification process for recombinant adeno-associated virus (raav). | adeno-associated virus (aav) is a human parvovirus currently being developed as a vector for gene therapy applications. traditionally aav has been purified from cell lysates using cscl gradients; this approach however is not likely to be useful in large-scale manufacturing. moreover gradient-purified aav vectors tend to be contaminated with significant levels of cellular and adenoviral proteins and nucleic acid. to address the issue of purification we have developed a process scale method for th ... | 2000 | 11199265 |
| evolutionary relationships among parvoviruses: virus-host coevolution among autonomous primate parvoviruses and links between adeno-associated and avian parvoviruses. | the current classification of parvoviruses is based on virus host range and helper virus dependence, while little data on evolutionary relationships among viruses are available. we identified and analyzed 472 sequences of parvoviruses, among which there were (virtually) full-length genomes of all 41 viruses currently recognized as individual species within the family parvoviridae. our phylogenetic analysis of full-length genomes as well as open reading frames distinguished three evolutionary gro ... | 2001 | 11222696 |
| attenuation of hypertension and heart hypertrophy by adeno-associated virus delivering angiotensinogen antisense. | angiotensinogen (agt), one of the major components in the renin-angiotensin system, has been linked to hypertension in humans and animals. we have previously systemically administered antisense oligonucleotides and plasmid vectors with dna that targeted agt and attenuated hypertension in spontaneously hypertensive rats. the aim of the present study was to prolong the effect of antisense treatment by the use of a recombinant adeno-associated viral (raav) vector targeted to agt. using a model of l ... | 2001 | 11230303 |
| aav-mediated delivery of ciliary neurotrophic factor prolongs photoreceptor survival in the rhodopsin knockout mouse. | retinitis pigmentosa (rp), an inherited retinal degenerative disease causing blindness, is characterized by progressive apoptotic death of photoreceptors. therapeutic modification of photoreceptor apoptosis may provide an effective therapy for this disorder. ciliary neurotrophic factor (cntf) has been shown to promote survival of a number of different neuronal cell types, including photoreceptors. the present study aimed to test whether adeno-associated virus (aav)-mediated delivery of the gene ... | 2001 | 11237681 |
| amino-terminal domain exchange redirects origin-specific interactions of adeno-associated virus rep78 in vitro. | the unique ability of adeno-associated virus type 2 (aav) to site-specifically integrate its genome into a defined sequence on human chromosome 19 (aavs1) makes it of particular interest for use in targeted gene delivery. the objective underlying this study is to provide evidence for the feasibility of retargeting site-specific integration into selected loci within the human genome. current models postulate that aav dna integration is initiated through the interactions of the products of a singl ... | 2001 | 11238849 |
| epitope-tagged recombinant aav vectors for expressing neurturin and its receptor in retinal cells. | neurturin (ntn) is a potent neuronal survival factor in the central and peripheral nervous systems. we previously described altered expression of mrnas for ntn and one of its receptor components, gfra-2 in degenerative retinas of rd/rd mice. towards assessing the potential for transfer of these genes to counteract retinal degeneration, we examined recombinant adeno-associated virus (raav) constructs for expression of ntn and gfra-2 transgenes in retinal cells in vitro and for the effect of trans ... | 2001 | 11239244 |
| gene therapy: a 2001 perspective. | in the past year, three clinical trials of gene therapy for haemophilia have been initiated. years of preclinical studies have culminated in translation of research findings into the clinical arena. it is too early to predict which, if any, of these strategies will show efficacy. this paper will review basic aspects of gene therapy for haemophilia and will briefly outline current clinical trials. the three clinical trials all share a dose escalation design. the ongoing trial for haemophilia b in ... | 2001 | 11240615 |
| efficient ex vivo transduction of pancreatic islet cells with recombinant adeno-associated virus vectors. | the ability to transfer immunoregulatory, cytoprotective, or antiapoptotic genes into pancreatic islet cells may allow enhanced posttransplantation survival of islet allografts and inhibition of recurrent autoimmune destruction of these cells in type 1 diabetes. however, transient transgene expression and the tendency to induce host inflammatory responses have limited previous gene delivery studies using viral transfer vectors. we demonstrate here that recombinant adeno-associated virus (raav) s ... | 2001 | 11246870 |
| antivector and antitransgene host responses in gene therapy. | current viral gene therapy vectors effectively transfer genes in vivo at the price of eliciting innate and acquired host responses against the vector and/or transgene. antigens present in the viral vector and the expression of the transgene both cause cellular and humoral immune responses dependent on the viral vector, the route of administration, and the genotype and infection history of the host. in general, adenoviral vectors cause strong immune responses, which result in only transient expre ... | 2000 | 11249767 |
| micro-injection-mediated hematopoietic stem cell gene therapy. | over the past decade, significant attention has been devoted to the development of viral vectors (i.e., retrovirus, lentivirus, adeno-associated virus) and conditions capable of transducing hematopoietic stem cells. after several years of disappointing results, recent reports in humans and other primates, most particularly the french report of successful treatment of x-linked severe combined immune deficiency (scid) [1.], indicate that viral approaches will be successful in treating specific hem ... | 2000 | 11249771 |
| herpes simplex virus-mediated gene transfer as a tool for neuropsychiatric research. | there is an enormous initiative to establish causal relationships between brain biology (including patterns of gene expression) and behavior. unfortunately, genetic intervention is not accomplished easily in the brain. one strategy is to engineer and deliver to the brain specialized viral vectors that carry a gene (or genes) of interest, thereby exploiting the natural ability of viruses to insert genetic information into cells. when delivered to the brain, these vectors cause infected cells to i ... | 2000 | 11253955 |
| [gene transfer--ways of administration, advantages, possible unsuitability and hazards]. | reports about successful gene therapy are now published after a period of more than ten years of trial and error. the key problem is to get dna from genes or gene fragments into the target cells to be transcribed. | 2001 | 11255867 |
| binding of adeno-associated virus type 5 to 2,3-linked sialic acid is required for gene transfer. | recombinant adeno-associated viruses (aav) are promising gene therapy vectors. whereas aav serotype 2-mediated gene transfer to muscle has partially replaced factor ix deficiency in hemophilia patients, its ability to mediate gene transfer to the lungs for cystic fibrosis is hindered by lack of apical receptors. however, aav serotype 5 infects human airway epithelia from the lumenal surface. we found that in contrast to aav2, the apical membrane of airway epithelia contains abundant high affinit ... | 2001 | 11262413 |
| cotransduction of tyrosine hydroxylase and aromatic l-amino acid decarboxylase genes into cultured striatal cells using adeno-associated virus vectors. | to examine whether tyrosine hydroxylase (th) and aromatic l-amino acid decarboxylase (aadc) genes can be cotransduced into the same target striatal cells using adeno-associated virus (aav) vectors, and to determine whether the cotransduction would result in better biochemical change than the th gene alone. | 1998 | 11263376 |
| gamma-rays enhance raav-mediated transgene expression and cytocidal effect of aav-hsvtk/ganciclovir on cancer cells. | adeno-associated virus (aav) vector has several unique properties suited for gene therapy applications. however, relatively low efficiency of transgene expression, which is mainly due to a limited second-strand synthesis from the single-stranded aav genome, can be a problem in some applications that require potent gene expression such as antitumor applications. recently, gamma-ray irradiation has been reported to enhance the second-strand synthesis of the aav genome, and consequently transgene e ... | 2001 | 11263531 |
| adeno-associated virus is associated with a lower risk of high-grade cervical neoplasia. | adeno-associated virus (aav) is a ubiquitous human helper-dependent parvovirus which may interact with human papillomaviruses (hpv) to modify a woman's risk of cervical neoplasia. this analysis was nested in a cohort study of low-income women receiving pap smears as part of their family planning services. we selected cases (55 with high-grade cervical squamous intraepithelial lesions (hsil) and 162 with low-grade lsil) and controls (96 women with normal cervical cytology) and analyzed cervical d ... | 2001 | 11263951 |
| cochlear gene delivery through an intact round window membrane in mouse. | cochlear gene transfer studies in animal models have utilized mainly two delivery methods: direct injection through the round window membrane (rwm) or intracochlear infusion through a cochleostomy. however, the surgical trauma, inflammation, and hearing loss associated with these methods lead us to investigate a less invasive delivery method. herein, we studied the feasibility of a vector transgene-soaked gelatin sponge, gelfoam, for transgene delivery into the mouse cochlea through an intact rw ... | 2001 | 11268286 |
| optimised helper virus-free production of high-quality adeno-associated virus vectors. | clinical development of adeno-associated virus (aav) requires standardised, safe, efficient and scalable procedures for the manufacture of the raav vector, including production, purification and testing. several strategies have been reported for the approach to the manufacturing problem. we report a helper virus-free process that produces high quality raav stocks. | 2001 | 11269337 |
| intracranial injection of recombinant adeno-associated virus improves cognitive function in a murine model of mucopolysaccharidosis type vii. | mucopolysaccharidosis type vii (mps vii) is a lysosomal storage disease caused by the lack of beta-glucuronidase (gusb) activity. gusb deficiency leads to the progressive accumulation of undegraded glycosaminoglycans (gags) in cells of most tissues, including the brain, and is associated with mental retardation. reduction of lysosomal storage in the central nervous system and prevention of cognitive dysfunction may require intracranial delivery of a therapeutic agent during the newborn period th ... | 2001 | 11273777 |
| effect of dna-dependent protein kinase on the molecular fate of the raav2 genome in skeletal muscle. | we report here that the dna-dependent protein kinase (dna-pk) affects the molecular fate of the recombinant adeno-associated virus (raav) genome in skeletal muscle. raav-human alpha1-antitrypsin (raav-haat) vectors were delivered by intramuscular injection to either c57bl/6 (dna-pkcs(+)) or c57bl/6-scid [severe combined immunodeficient (scid), dna-pkcs(-)] mice. in both strains, high levels of transgene expression were sustained for up to 1 year after a single injection. southern blot analysis s ... | 2001 | 11274433 |
| regulated secretion of proinsulin/insulin from human hepatoma cells transduced by recombinant adeno-associated virus. | to employ hepatocytes as surrogate beta-cells for gene therapy of diabetes, a regulatory system was devised in this study by placing the human insulin cdna under the control of the phosphoenolpyruvate carboxykinase (pepck) promoter, followed by the cytomegalovirus immediate early promoter-driven enhanced-green-fluorescent-protein open reading frame. the expression cassette was inserted into the adeno-associated virus vector between two inverted terminal repeats, and used to produce recombinant a ... | 2001 | 11277867 |
| suicide gene therapy for human oral squamous cell carcinoma cell lines with adeno-associated virus vector. | the purpose of this study was to test the possibility of gene transfer as a new therapy for oral cancer. adeno-associated virus (aav) has already been used in the fields of cystic fibrosis and parkinson's disease as a potential vector for gene therapy because of its wide host range, high transduction efficiency, and lack of cytopathogenicity. four human oral squamous cell carcinoma cell lines were transduced with an aav vector containing the beta-galactosidase gene (aavlacz) in vitro. gene trans ... | 2001 | 11287273 |
| adeno-associated virus type 2-mediated gene transfer: altered endocytic processing enhances transduction efficiency in murine fibroblasts. | adeno-associated virus type 2 (aav) is a single-stranded-dna-containing, nonpathogenic human parvovirus that is currently in use as a vector for human gene therapy. however, the transduction efficiency of aav vectors in different cell and tissue types varies widely. in addition to the lack of expression of the viral receptor and coreceptors and the rate-limiting viral second-strand dna synthesis, which have been identified as obstacles to aav-mediated transduction, we have recently demonstrated ... | 2001 | 11287557 |
| recombinant adeno-associated virus (raav) vector-mediated cotransduction of cd70 and cd80 into human malignant melanoma cells results in an additive t-cell response. | genetic modification of malignant melanoma cells by transduction of cdna encoding costimulatory molecules, cytokines or tumor-associated antigens has been shown to induce antitumor immunity. an important step in this scenario is the activation of t cells. cd80 is a pivotal costimulatory molecule for t-cell activation. another molecule with costimulatory activity is cd70. the purpose of this study was to evaluate the capacity of a combined expression of cd70 and cd80 on melanoma cells to amplify ... | 2001 | 11289576 |
| dual level inhibition of e2f-1 activity by adeno-associated virus rep78. | e2f-1, a major cellular transcription factor, plays a pivotal role in regulating the cell cycle. the activity of e2f-1 is negatively regulated by its interaction with retinoblastoma protein (prb), and disruption of the prb-e2f-1 complex, a hallmark of cellular transformation by dna tumor viruses, leads to cell proliferation. adeno-associated virus-2 (aav) is known to have onco-suppressive properties against dna tumor viruses. here we provide, for the first time, the molecular basis for antioncog ... | 2001 | 11294829 |
| integration of adeno-associated virus 2 dna in human mkr melanoma cells induces a peptide with oncosuppressive properties. | integration of adeno-associated virus type 2 (aav2) dna into the genome of the human mkr melanoma cell line grossly alters the cellular phenotype of these cells. cultures derived from aav dna-harboring single cells share various similarities with normal cells in culture, and a considerable number of clones show signs of cellular senescence and terminal differentiation. medium conditioned by such terminally differentiating cells contains a small cytokine-like factor (aav-induced factor [aif]). th ... | 2001 | 11304688 |
| enhanced expression and stable transmission of transgenes flanked by inverted terminal repeats from adeno-associated virus in zebrafish. | mosaic expression of transgenes in the f0 generation severely hinders the study of transient expression in transgenic fish. to avoid mosaicism, enhanced green fluorescent protein (egfp) gene cassettes were constructed and introduced into one-celled zebrafish embryos. these egfp gene cassettes were flanked by inverted terminal repeats (itrs) from adeno-associated virus (aav) and driven by zebrafish alpha-actin (palpha-actin-egfp-itr) or medaka beta-actin promoters (pbeta-actin-egfp-itr). egfp was ... | 2001 | 11307166 |
| two animal models of retinal degeneration are rescued by recombinant adeno-associated virus-mediated production of fgf-5 and fgf-18. | the goal of these experiments was to evaluate the potential of the fibroblast growth factor family members fgf-5 and fgf-18 to rescue photoreceptors from cell death in retinal degenerative disease. two strains of transgenic rats, expressing either a p23h or an s334ter rhodopsin mutation, were used as model systems. the neurotrophic growth factors were delivered by subretinal injection of adeno-associated virus vectors, driving expression of the genes with a constitutive cmv promoter. morphologic ... | 2001 | 11319911 |
| introduction of single base substitutions at homologous chromosomal sequences by adeno-associated virus vectors. | adeno-associated virus (aav) vectors can modify homologous chromosomal sequences at high rates. this gene targeting transduction pathway is distinct from the integrating and episomal pathways used in gene addition approaches. in previous studies, aav vectors were used to introduce small insertion and deletion mutations at homologous chromosomal loci. here we show that aav-mediated gene targeting can also be used to introduce all possible types of single base substitution mutations at the endogen ... | 2001 | 11319913 |
| the role of receptors in the maturation-dependent adenoviral transduction of myofibers. | one of the major hurdles facing the application of adenoviral gene transfer to skeletal muscle is the maturation-dependent transduction of muscle myofibers. it was recently proposed that the viral receptors (coxsackie and adenovirus receptor (car) and the integrins alphavbeta3/beta5) play a major role in the poor adenoviral transduction of mature myofibers. here we report the findings of morphological studies designed to determine experimentally the role of receptors in the adenoviral transducti ... | 2001 | 11320409 |
| gene therapy restores vision in a canine model of childhood blindness. | the relationship between the neurosensory photoreceptors and the adjacent retinal pigment epithelium (rpe) controls not only normal retinal function, but also the pathogenesis of hereditary retinal degenerations. the molecular bases for both primary photoreceptor and rpe diseases that cause blindness have been identified. gene therapy has been used successfully to slow degeneration in rodent models of primary photoreceptor diseases, but efficacy of gene therapy directed at photoreceptors and rpe ... | 2001 | 11326284 |
| distribution of albumin nanoparticles in animals induced with the experimental allergic encephalomyelitis. | experimental allergic encephalomyelitis (eae) is an autoimmune disease characterised by a disruption of the blood-brain barrier (bbb), demyelination and a relevant inflammatory reaction with an intense infiltration of macrophages. these neurological disorders are similar to those observed in the multiple sclerosis (ms) disease. the use of different liposomes and adeno-associated virus has been proposed for improving the treatment of this pathogenesis. the aim of this work was to evaluate the pot ... | 2000 | 11328657 |
| a rep recognition sequence is necessary but not sufficient for nicking of dna by adeno-associated virus type-2 rep proteins. | the strand-specific, site-specific endonuclease (nicking) activity of the rep68 and rep78 (rep68/78) proteins of adeno-associated virus type 2 (aav) is involved in aav replication, and appears to be involved in aav site-specific integration. rep68/78 cuts within the inverted terminal repeats (itrs) of the aav genome and in the aav preferred integration locus on human chromosome 19 (aavs1). the known endonuclease cut sites are 11-16 bases away from the primary binding sites, known as rep recognit ... | 2001 | 11339817 |
| cochlear function and transgene expression in the guinea pig cochlea, using adenovirus- and adeno-associated virus-directed gene transfer. | development of a viral vector that can infect hair cells of the cochlea without producing viral-associated ototoxic effects is crucial for utilizing gene replacement therapy as a treatment for certain forms of hereditary deafness. in the present study, cochlear function was monitored using distortion-product otoacoustic emissions (dpoaes) in guinea pigs that received infusions of either (e1(-), e3(-)) adenovirus, or adeno-associated virus (aav), directly into the scala tympani. replication-defic ... | 2001 | 11339894 |
| induction of tolerance to human factor viii in mice. | this paper reports loss of human factor viii (hfviii) inhibitory antibody in immunocompetent c57bl/6 mice. high-titer anti-hfviii antibody developed in the mice within 7 to 14 days of intraportal administration of adeno-associated virus (aav) carrying fviii that coincided with a reduction in plasma hfviii antigen. bethesda titers (> 100 units) persisted relatively unchanged for 9 to 10 months. unexpectedly, at 10 months after injection of the virus, hfviii protein (up to 59 ng/ml) was detected i ... | 2001 | 11342466 |
| use of perfluorochemical liquid allows earlier detection of gene expression and use of less vector in normal lung and enhances gene expression in acutely injured lung. | one of the obstacles to successful lung gene transfer is effective delivery of vector to lung, particularly injured or diseased lung. we have previously demonstrated that intratracheal instillation of perfluorochemical (pfc) liquids along with instillation of recombinant adenovirus and adeno-associated virus vectors, or with cationic liposome vectors, increased total lung gene expression and enhanced distribution of gene expression throughout the lung. to further explore the potential benefits o ... | 2001 | 11356078 |
| generation of recombinant adeno-associated virus vectors by a complete adenovirus-mediated approach. | an efficient approach to the large-scale production of raav will significantly facilitate the application of this promising gene delivery vector in human gene therapy applications. in this study, we report a novel approach to raav production that is based exclusively on the adenovirus vector, without the need for plasmid transfections and special packaging cell lines. all components required for raav production, including the rep and cap genes, and the therapeutic gene(s) are delivered to the wi ... | 2001 | 11356083 |
| gene transfer into neurons from hippocampal slices: comparison of recombinant semliki forest virus, adenovirus, adeno-associated virus, lentivirus, and measles virus. | viral vectors are useful for transferring genes into neurons. here, we characterized recombinant semliki forest virus (sfv), adenovirus type 5 (ad5), adeno-associated virus type 2 (aav), lentivirus, and measles virus (mv) by their expression of green fluorescent protein (gfp) in rat hippocampal slice cultures. sfv infected more neurons (>90% of all gfp-positive cells) than aav, lentivirus, and mv (71, 69, and 62%, respectively), whereas no infected neurons were identified with ad5. aav-mediated ... | 2001 | 11358483 |
| the effect of adeno-associated virus mediated brain derived neurotrophic factor in an animal model of neurogenic impotence. | we tested the hypothesis that transfecting penile tissue with brain derived neurotrophic factor may facilitate neural recovery and erectile capability after cavernous nerve injury. | 2001 | 11371936 |
| central leptin gene therapy suppresses body weight gain, adiposity and serum insulin without affecting food consumption in normal rats: a long-term study. | the weight-reducing effects of leptin are predominantly mediated through the hypothalamus in the brain. gene therapy strategies designed for weight control have so far tested the short-term effect of peripherally delivered viral vectors encoding the leptin gene. in order to circumvent the multiple peripheral effects of hyperleptinemia and to overcome the age-related development of leptin resistance due to multiple factors, including defective leptin transport across the blood brain barrier, we d ... | 2001 | 11384767 |
| factors influencing the development of an anti-factor ix (fix) immune response following administration of adeno-associated virus-fix. | the present study sought to determine the impact of the route of administration of an adeno-associated virus (aav) vector encoding human factor ix (hfix) on the induction of an immune response against the vector and its xenogenic transgene product, hfix. increasing doses of aav-hfix were administered by different routes to c57bl/6 mice, which typically demonstrate significant immune tolerance to hfix. the route of delivery had a profound impact on serum hfix levels as well as the induction of an ... | 2001 | 11389010 |
| hybrid vectors based on adeno-associated virus serotypes 2 and 5 for muscle-directed gene transfer. | vectors based on hybrids consisting of adeno-associated virus types 2 (itrs and rep) and 5 (cap) were evaluated for muscle-directed gene transfer (called aav2/5). evaluation in immune-competent mice revealed greater transduction efficacy with aav2/5 than with aav2 and no cross-neutralization between aav2/5 and aav2. interestingly, we saw no immunologic evidence of previous exposure to aav5 capsids in a large population of healthy human subjects. | 2001 | 11390622 |
| morphological and physiological restorations of hereditary form of dilated cardiomyopathy by somatic gene therapy. | to-2 strain hamsters with dilated cardiomyopathy, gene deletion of delta-sarcoglycan (sg) and no expression of alpha-, beta-, gamma-, and delta-sg proteins are useful for developing the potential gene therapy of intractable heart failure. we prepared recombinant adeno-associated virus vector including normal delta-sg gene driven by cmv promoter and intramurally administered in vivo. the transfected myocardium induced robust expression of both transcript and transgene for 2/3 period of the animal ... | 2001 | 11394897 |
| a novel recombinant adeno-associated virus vaccine induces a long-term humoral immune response to human immunodeficiency virus. | recombinant adeno-associated virus (aav) has attracted tremendous interest as a promising vector for gene delivery. in this study we have developed an hiv-1 vaccine, using an aav vector expressing hiv-1 env, tat, and rev genes (aav-hiv vector). a single injection of the aav-hiv vector induced strong production of hiv-1-specific serum igg and fecal secretory iga antibodies as well as mhc class i-restricted ctl activity in balb/c mice. the titer of hiv-1-specific serum igg remained stable for 10 m ... | 2001 | 11399227 |
| in vivo myocardial gene transfer: optimization, evaluation and direct comparison of gene transfer vectors. | the purpose was to determine the relative efficiency, toxicity and duration of expression following gene delivery by intramyocardial injection of naked dna, naked dna complexed to cationic liposomes, naked dna complexed to cationic liposomes with integrin-targetting peptide, recombinant (e1-/e3-) adenovirus, recombinant adeno-associated virus and recombinant (icp27-) herpes simplex virus. all vectors incorporated a lacz reporter driven by a promoter containing the hcmv-ie promoter/enhancer. effi ... | 2001 | 11403416 |
| dna helicase-mediated packaging of adeno-associated virus type 2 genomes into preformed capsids. | helicases not only catalyse the disruption of hydrogen bonding between complementary regions of nucleic acids, but also move along nucleic acid strands in a polar fashion. here we show that the rep52 and rep40 proteins of adeno-associated virus type 2 (aav-2) are required to translocate capsid-associated, single-stranded dna genomes into preformed empty aav-2 capsids, and that the dna helicase function of rep52/40 is essential for this process. furthermore, dnase protection experiments suggest t ... | 2001 | 11406604 |
| recombinant adenovirus expressing adeno-associated virus cap and rep proteins supports production of high-titer recombinant adeno-associated virus. | it has been difficult to produce a chimeric vector containing both ad and aav rep and cap, and to grow such chimeric vectors in 293 cells. by recombination in vitro in a bacterial host, we were able to produce recombinant plasmid adaav (padaavrep-cap), which could be used to generate recombinant adaav (radaavrep-cap) after transfection into 293 cells. a recombinant adenovirus, radaavgfp, in which the green fluorescent protein (gfp) gene is flanked by the aav terminal repeats cloned into the e1-d ... | 2001 | 11406765 |
| adeno-associated virus 2-mediated transduction and erythroid lineage-restricted long-term expression of the human beta-globin gene in hematopoietic cells from homozygous beta-thalassemic mice. | adeno-associated virus 2 (aav), a nonpathogenic human parvovirus, has gained attention as a potentially useful vector for human gene therapy. here, we report successful aav-mediated stable transduction and high-efficiency, long-term, erythroid lineage-restricted expression of a human beta-globin gene in primary murine hematopoietic stem cells in vivo. bone marrow-derived primitive sca-1(+), lin(-) hematopoietic stem cells from homozygous beta-thalassemic mice were transduced ex vivo with a recom ... | 2001 | 11407908 |
| incorporation of tumor-targeting peptides into recombinant adeno-associated virus capsids. | the human parvovirus adeno-associated virus type 2 (aav-2) possesses many features that make it an attractive vector for gene delivery in vivo. however, its broad host range may limit its usefulness and effectivity in several gene therapy applications in which transgene expression needs to be limited to a specific organ or cell type. in this study, we explored the possibility of directing recombinant aav-2 transduction by incorporating targeting peptides previously isolated by in vivo phage disp ... | 2001 | 11407911 |
| adeno-associated virus type 6 (aav6) vectors mediate efficient transduction of airway epithelial cells in mouse lungs compared to that of aav2 vectors. | although vectors derived from adeno-associated virus type 2 (aav2) promote gene transfer and expression in many somatic tissues, studies with animal models and cultured cells show that the apical surface of airway epithelia is resistant to transduction by aav2 vectors. approaches to increase transduction rates include increasing the amount of vector and perturbing the integrity of the epithelia. in this study, we explored the use of vectors based on aav6 to increase transduction rates in airways ... | 2001 | 11413329 |
| standard heparin, low molecular weight heparin, low molecular weight heparinoid, and recombinant hirudin differ in their ability to inhibit transduction by recombinant adeno-associated virus type 2 vectors. | recombinant adeno-associated virus type 2 (raav) is a promising vector for in vivo gene therapy. transduction by raav requires binding to heparan sulfate proteoglycan on the cell surface, and heparin can block this binding. because heparin is administered to most patients undergoing cardiovascular gene transfer in order to prevent thrombotic events, it is important to identify anticoagulants which do not interfere with raav transduction. therefore, we examined the influence of different anticoag ... | 2001 | 11426338 |
| kinetics of efficient recombinant adeno-associated virus transduction in retinal pigment epithelial cells. | the aim of this study was to investigate the premise that retinal pigment epithelial (rpe) cells are more permissive to recombinant adeno-associated virus (raav) transduction than other cells. we investigated the kinetics and mechanisms of raav transduction in rpe cells and found that the transduction efficiencies of cultured rpe cells hrpe51 and arpe19 were significantly higher than those of 293 (p < 0.008) and hela (p < 0.025) cells. in addition, rpe cells reached maximum transduction efficien ... | 2001 | 11426937 |
| adeno-associated virus serotype 4 (aav4) and aav5 both require sialic acid binding for hemagglutination and efficient transduction but differ in sialic acid linkage specificity. | adeno-associated virus serotype 4 (aav4) and aav5 have different tropisms compared to aav2 and to each other. we recently reported that alpha 2--3 sialic acid is required for aav5 binding and transduction. in this study, we characterized aav4 binding and transduction and found it also binds sialic acid, but the specificity is significantly different from aav5. aav4 can hemagglutinate red blood cells from several species, whereas aav5 hemagglutinates only rhesus monkey red blood cells. treatment ... | 2001 | 11435568 |
| extrachromosomal recombinant adeno-associated virus vector genomes are primarily responsible for stable liver transduction in vivo. | recombinant adeno-associated virus (raav) vectors stably transduce hepatocytes in experimental animals. although the vector genomes are found both as extrachromosomes and as chromosomally integrated forms in hepatocytes, the relative proportion of each has not yet been clearly established. using an in vivo assay based on the induction of hepatocellular regeneration via a surgical two-thirds partial hepatectomy, we have determined the proportion of integrated and extrachromosomal raav genomes in ... | 2001 | 11435577 |
| convection-enhanced delivery of aav-2 combined with heparin increases tk gene transfer in the rat brain. | adeno-associated virus type2 (aav-2) binds to heparan-sulfate proteoglycans on the cell surface. in vivo, attachment of viral particles to cells adjacent to the injection tract limits the distribution of aav-2 when infused into the cns parenchyma and heparin co-infusion might decrease the binding of aav-2 particles to cells in the vicinity of the infusion tract. we have previously shown that heparin co-infusion combined with convection enhanced delivery enhances distribution of the gdnf family t ... | 2001 | 11435930 |
| factors influencing cross-presentation of non-self antigens expressed from recombinant adeno-associated virus vectors. | we have previously demonstrated that recombinant adeno-associated virus vectors expressing the influenza virus hemagglutinin (raav-ha) in skeletal muscle results in t-cell priming and muscle fiber destruction due to cross-presentation of ha by dendritic cells (dc). based on controversial observations concerning the stability of non-self proteins expressed from raav vectors it is important to understand the factors influencing cross-presentation of transgene products following raav mediated gene ... | 2001 | 11437331 |
| optimization of recombinant adeno-associated virus production using an herpes simplex virus amplicon system. | a major limitation of adeno-associated virus (aav) based vectors for clinical applications to date is the production of high-titer recombinant aav vector stocks. despite recent improvements, the amount of recombinant adeno-associated virus vectors (raav) particles produced per cell continues to be significantly lower than that of wild-type aav. in this study, an hsv-based system for raav production was used to examine the influence of different parameters including transfection conditions (vecto ... | 2001 | 11445141 |
| enhancement of muscle gene delivery with pseudotyped adeno-associated virus type 5 correlates with myoblast differentiation. | adeno-associated virus (aav)-based muscle gene therapy has achieved tremendous success in numerous animal models of human diseases. recent clinical trials with this vector have also demonstrated great promise. however, to achieve therapeutic benefit in patients, large inocula of virus will likely be necessary to establish the required level of transgene expression. for these reasons, efforts aimed at increasing the efficacy of aav-mediated gene delivery to muscle have the potential for improving ... | 2001 | 11462038 |
| gene therapy and retinitis pigmentosa: advances and future challenges. | it may be possible, one day, to use gene therapy to treat diseases whose genetic defects have been discerned. because many genes responsible for inherited eye disorders within the retina have been identified, diseases of the eye are prime candidates for this form of therapy. the eye also has the advantage of being highly accessible with altered immunological properties, important considerations for easy delivery of virus and avoidance of systemic immune responses. currently, adenovirus, adeno-as ... | 2001 | 11462220 |
| methods for adeno-associated virus-mediated gene transfer into muscle. | | 2001 | 11462851 |
| detection of adeno-associated virus dna in female genital samples by pcr-elisa. | adeno-associated viruses (aav) are human parvoviruses that require helper function for their replication. several studies have demonstrated that aav dna sequences can be found in the female genital tract but the incidence of infection seems very variable. a pcr-elisa method detecting aav dna was developed for combining the specificity and the sensitivity of conventional pcr with an objective interpretation of the results. in the pcr-elisa, a defined number of cells from cervical specimens were d ... | 2001 | 11468746 |
| detection of cervical infections in colposcopy clinic patients. | the purpose of this study was to determine if neisseria gonorrhoeae; chlamydia trachomatis; herpes simplex virus; cytomegalovirus; epstein-barr virus; human herpesviruses 6, 7, and 8; or adeno-associated virus influenced the production of cervical intraepithelial neoplasia. two hundred thirty-one cervical smear samples were tested for the presence of the organisms by pcr. in addition, human papillomavirus types in the samples were determined by pcr and classified into cancer risk types of high, ... | 2001 | 11474018 |