Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
|---|
| 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 |
| 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 |
| 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 |
| long-term systemic therapy of fabry disease in a knockout mouse by adeno-associated virus-mediated muscle-directed gene transfer. | fabry disease is a systemic disease caused by genetic deficiency of a lysosomal enzyme, alpha-galactosidase a (alpha-gal a), and is thought to be an important target for enzyme replacement therapy. we studied the feasibility of gene-mediated enzyme replacement for fabry disease. the adeno-associated virus (aav) vector containing the alpha-gal a gene was injected into the right quadriceps muscles of fabry knockout mice. a time course study showed that alpha-gal a activity in plasma was increased ... | 2002 | 12370426 |
| gene marking in adeno-associated virus vector infected periosteum derived cells for cartilage repair. | to evaluate both the potential for transferring genes to periosteal cells using an adeno-associated virus (aav) vector and the potential for gene expression after transplantation of those cells to a cartilage defect in vivo. | 2002 | 12375329 |
| the adeno-associated virus crystal: impact inversely proportional to size. | 2002 | 12377184 | |
| therapeutic liabilities of in vivo viral vector tropism: adeno-associated virus vectors, nmdar1 antisense, and focal seizure sensitivity. | the n-methyl-d-aspartic acid (nmda) receptor provides a potential target for gene therapy of focal seizure disorders. to test this approach, we cloned a 729-bp nmda receptor (nmdar1) cdna fragment in the antisense orientation into adeno-associated virus (aav) vectors, where expression was driven by either a tetracycline-off regulatable promoter (aav-ttak-nr1a) or a cytomegalovirus (cmv) promoter (aav-cmv-nr1a). after infection of primary cultured cortical neurons with recombinant aav-ttak-nr1a, ... | 2002 | 12377191 |
| production of recombinant adeno-associated type 5 (raav5) vectors using recombinant herpes simplex viruses containing rep and cap. | we developed a scaleable production system for adeno-associated virus type 5 (aav5)-based vectors using a replication-defective recombinant herpes simplex type 1 virus (rhsv) containing the rep and cap genes of aav5. multiple rhsv isolates containing aav5 rep and cap with normal or altered p5 promoter elements were constructed and tested in vector production. compared with raav5 vector yields obtained by plasmid transfection, yields of raav5 using any of the rhsv isolates were low. evidence sugg ... | 2002 | 12377193 |
| deposition and expression of aerosolized raav vectors in the lungs of rhesus macaques. | the goals of these experiments were to efficiently deliver aerosolized adeno-associated virus (aav) vector to the lungs of rhesus macaques and to measure gene transfer and expression. to determine optimal lung deposition, we compared four techniques of delivering aerosolized saline admixed with the radioisotope (99m)technetium ((99m)tc) nebulized through a mouthpiece (neb oral), a laryngeal airway mask (neb lma), or an endotracheal tube (neb ett), or bronchoscopically delivered by microsprayer ( ... | 2002 | 12387250 |
| a limited number of transducible hepatocytes restricts a wide-range linear vector dose response in recombinant adeno-associated virus-mediated liver transduction. | recombinant adeno-associated virus (raav) vectors are promising vehicles for achieving stable liver transduction in vivo. however, the mechanisms of liver transduction are not fully understood, and furthermore, the relationships between raav dose and levels of transgene expression, total number of hepatocytes transduced, and proportion of integrated vector genomes have not been well established. to begin to elucidate the liver transduction dose response with raav vectors, we injected mice with t ... | 2002 | 12388694 |
| adenovirus-facilitated nuclear translocation of adeno-associated virus type 2. | we examined cytoplasmic trafficking and nuclear translocation of adeno-associated virus type 2 (aav) by using alexa fluor 488-conjugated wild-type aav, a20 monoclonal antibody immunocytochemistry, and subcellular fractionation techniques followed by dna hybridization. our results indicated that in the absence of adenovirus (ad), aav enters the cell rapidly and escapes from early endosomes with a t(1/2) of about 10 min postinfection. cytoplasmically distributed aav accumulated around the nucleus ... | 2002 | 12388712 |
| cell-type-specific characteristics modulate the transduction efficiency of adeno-associated virus type 2 and restrain infection of endothelial cells. | adeno-associated viruses (aavs) are promising vectors for various gene therapy applications due to their long-lasting transgene expression and wide spectrum of target cells. recently, however, it has become apparent that there are considerable differences in the efficiencies of transduction of different cell types by aavs. here, we analyzed the efficiencies of transduction and the transport mechanisms of aav type 2 (aav-2) in different cell types, emphasizing endothelial cells. expression analys ... | 2002 | 12388714 |
| lack of an immune response against the tetracycline-dependent transactivator correlates with long-term doxycycline-regulated transgene expression in nonhuman primates after intramuscular injection of recombinant adeno-associated virus. | we previously documented persistent regulation of erythropoietin (epo) secretion in mice after a single intramuscular (i.m.) injection of a recombinant adeno-associated virus (raav) vector harboring both the tetracycline-dependent transactivator (rtta) and the epo cdna (d. bohl, a. salvetti, p. moullier, and j. m. heard, blood 92:1512-1517, 1998). using the same vector harboring the cynomolgus macaque epo cdna instead, the present study evaluated the ability of the tetracycline-regulatable (tetr ... | 2002 | 12388721 |
| muscle derived cell mediated ex vivo gene transfer to the lower urinary tract: comparison of viral vectors. | gene therapy is a novel form of molecular medicine that may have a major impact on the future of human health care. we explored the efficacy of skeletal muscle derived cells (mdc) transduced with four viruses for ex vivo gene transfer into the lower urinary tract. primary mdc were isolated from normal neonatal rats and transduced with: (1). adenovirus, (2). herpes simplex virus type-1 (hsv-1), (3). retrovirus or (4). adeno-associated virus (aav), all of which express the beta-galactosidase repor ... | 2002 | 12389119 |
| gene therapy for spinal applications. | gene therapy is a promising drug delivery mechanism for the treatment of spinal disorders. currently, the technique has been most useful in enhancing growth factor therapy for spinal fusion, intervertebral disc regeneration, and spinal cord injury healing. gene therapy allows for the high-level local production of growth factors, obviating the need for slow release carriers or continuous infusion pumps that are otherwise necessary because of the short half-lives of most peptide growth factors. a ... | 2002 | 12389290 |
| transneuronal tracing of diverse cns circuits by cre-mediated induction of wheat germ agglutinin in transgenic mice. | systems neuroscience addresses the complex circuits made by populations of neurons in the cns and the cooperative function of these neurons. improved approaches to the neuroanatomical analysis of cns circuits are thus of great interest. in fact, significant advances in tract-tracing methods have recently been made by using transgenic mice that express transneuronal lectin tracers under the control of neuron-specific promoters. the utility of those animals, however, is limited to the cns circuit ... | 2002 | 12391304 |
| evidence for the existence of distinct central appetite, energy expenditure, and ghrelin stimulation pathways as revealed by hypothalamic site-specific leptin gene therapy. | to identify the specific hypothalamic sites in which leptin acts to decrease energy intake and/or increase energy expenditure, recombinant adeno-associated virus vector-encoding leptin was microinjected bilaterally into one of four hypothalamic sites in female rats. leptin transgene expression in the ventromedial nucleus and paraventricular nucleus induced comparable decreases in daily food intake (fi; 18-20%) and body weight (bw; 26-29%), accompanied by drastic reductions in serum leptin (81-97 ... | 2002 | 12399438 |
| gene therapy for detached retina by adeno-associated virus vector expressing glial cell line-derived neurotrophic factor. | to examine the protective effect of glial cell line-derived neurotrophic factor (gdnf) on retinal detachment (rd)-induced photoreceptor damage by using gene delivery. | 2002 | 12407159 |
| hypothalamic delivery of doxycycline-inducible leptin gene allows for reversible transgene expression and physiological responses. | our purpose was to incorporate regulation into the recombinant adeno-associated virus encoding leptin by introducing a tet-inducible promotor. this system, tet-ob, allows for control of leptin gene expression via doxycycline in drinking water. f344xbn rats (aged 4 months) were given a hypothalamic injection of tet-ob or control virus. during 34 days of doxycycline (doxy) administration to all rats (stage 1), tet-ob rats gained 50.7% less mass, ate 10.4% less food, and had a 77.5% reduction in se ... | 2002 | 12407421 |
| production methods for gene transfer vectors based on adeno-associated virus serotypes. | vectors derived from adeno-associated virus serotype 2 (aav-2) represent a most promising tool for human gene transfer because these vectors are neither pathogenic nor toxic to the target cell, and allow long-term gene expression in a large variety of tissues. however, they are rather inefficient at infecting a number of clinically relevant cell types, and transduction by these vectors is likely hampered by neutralizing antibodies that are highly prevalent in the human population. therefore, an ... | 2002 | 12413413 |
| adeno-associated viral vectors as agents for gene delivery: application in disorders and trauma of the central nervous system. | the use of viral vectors as agents for gene delivery provides a direct approach to manipulate gene expression in the mammalian central nervous system (cns). the present article describes in detail the methodology for the injection of viral vectors, in particular adeno-associated virus (aav) vectors, into the adult rat brain and spinal cord to obtain reproducible and successful transduction of neural tissue. surgical and injection procedures are based on the extensive experience of our laboratory ... | 2002 | 12413416 |
| application of adeno-associated viral vectors in behavioral research. | viral vectors afford the capability of genetically manipulating the expression of neurotransmitters, neuropeptides, hormones, and their receptors in specific brain sites of adult animals of any species. hence, they are a powerful tool for investigating the neurochemistry underlying complex cognitive processes and behaviors. here we discuss how the recombinant adeno-associated virus (raav) can be engineered for use in neurobehavioral studies, techniques for site-specific delivery of vector into t ... | 2002 | 12413417 |
| adeno-associated virus-mediated gene transfer to the neonatal brain. | for many metabolic diseases, early treatment is necessary to prevent irreversible developmental damage. this is particularly true for childhood diseases that affect the central nervous system (cns). the development of effective techniques for gene transfer to the neonatal brain would provide a new set of therapeutic options for many of these disorders. vectors based on adeno-associated virus (aav) have shown promise as agents for neonatal cns transduction. in preclinical animal models, a single ... | 2002 | 12413418 |
| recombinant adeno-associated virus vector design and gene expression in the mammalian brain. | efficiency and stability of recombinant adeno-associated virus (raav)-mediated gene expression within the mammalian brain are determined by several factors. these include the dose of infectious particles, the purity of the vector stock, the serotype of raav, the route of administration, and the intrinsic properties, most notably the raav receptor density, of the targeted area. furthermore, the choice of appropriate regulatory elements in raav vector design is of fundamental importance to achieve ... | 2002 | 12413419 |
| regulation of gene expression in adeno-associated virus vectors in the brain. | regulated adeno-associated virus (aav) vectors have broad utility in both experimental and applied gene therapy, and to date, several regulation systems have exhibited a capability to control gene expression from viral vectors over two orders of magnitude. the tetracycline responsive system has been the most used in aav, although other regulation systems such as ru486- and rapamycin-responsive systems are reasonable options. aav vectors influence how regulation systems function by several mechan ... | 2002 | 12413420 |
| promoters and regulatory elements that improve adeno-associated virus transgene expression in the brain. | since the first demonstration of central nervous system (cns) transduction with recombinant adeno-associated virus, improvements in vector production and promoter strength have lead to dramatic increases in the number of cells transduced and the level of expression within each cell. the improvements in promoter strength have resulted from a move away from the original cytomegalovirus (cmv) promoter toward the use of hybrid cmv-based promoters and constitutive cellular promoters. this review summ ... | 2002 | 12413421 |
| adeno-associated virus vectors for gene transfer to the brain. | gene therapy is a novel method under investigation for the treatment of neurological disorders. considerable interest has focused on the possibility of using viral vectors to deliver genes to the central nervous system. adeno-associated virus (aav) is a potentially useful gene transfer vehicle for neurologic gene therapies. the advantages of aav vector include the lack of any associated disease with a wild-type virus, the ability to transduce nondividing cells, the possible integration of the ge ... | 2002 | 12413422 |
| adeno-associated virus-mediated antiapoptotic gene delivery: in vivo gene therapy for neurological disorders. | apoptosis is an important mechanism of physiological and pathological cell death and is known to occur in various neurological disorders. apoptosis is associated with activation of genetic programs in which apoptosis-effector genes promote cell death, thereby opposing repressor genes that enhance cell survival. in this review, we describe various apoptotic pathways, with a special reference to the caspase cascade and discuss the role of individual antiapoptotic factors in various target diseases ... | 2002 | 12413423 |
| gene therapy for treatment of cerebral ischemia using defective recombinant adeno-associated virus vectors. | in this review we present our results and experiences in performing gene therapy of cerebral stroke using recombinant adeno-associated virus (raav) vectors in a rat model. the methodologies involving the production of aav vectors, gene transfer to the brain, and a trivessel ligation model of focal ischemic cerebral stroke in rats are described. furthermore, a brief description of other viral vectors and candidates of therapeutic transgenes used for gene therapy of cerebral stroke are presented. ... | 2002 | 12413424 |
| vigilant vectors: adeno-associated virus with a biosensor to switch on amplified therapeutic genes in specific tissues in life-threatening diseases. | there are many life-threatening and chronic diseases in which physiological signals could be used to switch on therapeutic protective genes. we are developing a gene therapy approach in which a systemically injected "vigilant vector" waits for these signals and switches on genes to protect specific tissues with high amplification. the concept of a vigilant vector requires four components. the first component is a safe and stable vector that can be administered by systemic injection and express t ... | 2002 | 12413425 |
| gene delivery to the eye using adeno-associated viral vectors. | adeno-associated virus (aav) vectors provide a useful way to deliver genes to the eye. they have a number of important properties which make them suitable for this purpose, not least their lack of significant pathogenicity and the potential for long-term transfection of retinal cells. the optimal methods for aav-mediated gene delivery are determined by the location and characteristics of the target cell type. efficient gene delivery to photoreceptors and pigment epithelial cells following subret ... | 2002 | 12413426 |
| measurements of vector-derived neurotrophic factor and green fluorescent protein levels in the brain. | demonstrating consistently reliable levels of expression is a critical part of any gene transfer study in order to assess variability and determine effective gene dosages. this article highlights some of the key methods for studying the expression levels of green fluorescent protein and neurotrophic factors after injections of adeno-associated virus (aav) vectors into the brain. the data demonstrate greater spread and higher levels of expression using the cytomegalovirus/chicken beta-actin (cba) ... | 2002 | 12413428 |
| addition of six-his-tagged peptide to the c terminus of adeno-associated virus vp3 does not affect viral tropism or production. | production of large quantities of recombinant adeno-associated virus (aav) is difficult and not cost-effective. to overcome this problem, we have explored the feasibility of creating a recombinant aav encoding a 6xhis tag on the vp3 capsid protein. we generated a plasmid vector containing a six-his (6xhis)-tagged aav vp3. a second plasmid vector was generated that contained the full-length aav capsid capable of producing vp1 and vp2, but not vp3 due to a mutation at position 2809 that encodes th ... | 2002 | 12414944 |
| adeno-associated virus vector-mediated gene transfer into dystrophin-deficient skeletal muscles evokes enhanced immune response against the transgene product. | duchenne muscular dystrophy (dmd) is an x-linked, lethal muscular disorder caused by a defect in the dmd gene. aav vector-mediated micro-dystrophin cdna transfer is an attractive approach to treatment of dmd. to establish effective gene transfer into skeletal muscle, we examined the transduction efficiency of an aav vector in skeletal muscles of dystrophin-deficient mdx mice. when an aav vector encoding the lacz gene driven by a cmv promoter (aav-cmvlacz) was introduced, beta-galactosidase expre ... | 2002 | 12424610 |
| insect cells as a factory to produce adeno-associated virus type 2 vectors. | recombinant adeno-associated viruses (raav) are produced transiently in mammalian cells usually by cotransfecting two or three plasmids containing aav genes, adenovirus helper genes, and a vector genome. expansion and transfection of adherent cells limit the scale of raav production. efficient transfection is performed with cells on solid support media such as tissue culture plates. a large animal study or a human clinical trial may require 10(15) particles of vector, depending on dose. to gener ... | 2002 | 12427305 |
| alphaviral vectors for gene transfer into neurons. | alphaviruses are small, enveloped positive-strand rna viruses that have been successfully transformed into expression vectors in the case of semliki forest virus (sfv), sindbis virus (sin), and venezuelan equine encephalitis virus. compared to other viral vectors, their advantages are easy and fast generation of recombinant viral particles, rapid onset, and high-level transgene expression. when applied to neuronal tissue, sfv and sin vectors possess the additional advantage of efficiently and pr ... | 2002 | 12428755 |
| plasmid delivery in the rat brain. | neurodegenerative diseases as a class do not have effective pharmacotherapies. this is due in part to a poor understanding of the pathologies of the disease processes, and the lack of effective medications. gene delivery is an attractive possibility for treating these diseases. for the paradigm to be effective, efficient, safe and versatile vectors are required. in this study we evaluated three plasmid delivery systems for transgene expression in the rat hippocampus. two of these systems were de ... | 2002 | 12428906 |
| suppression of insult-induced neurogenesis in adult rat brain by brain-derived neurotrophic factor. | in mammals, including humans, the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus contain neural stem cells, which continue to proliferate even in adulthood and give rise to new neurons. neurogenesis in these areas is enhanced by brain insults. brain-derived neurotrophic factor (bdnf) promotes neuronal survival and differentiation during the development of the nervous system. in the adult intact brain, bdnf administration in the lateral ventricle or ven ... | 2002 | 12429205 |
| a versatile and scalable two-step ion-exchange chromatography process for the purification of recombinant adeno-associated virus serotypes-2 and -5. | here we describe the development of a two-step chromatography process based on the use of ion-exchange resins for the purification of recombinant adeno-associated virus (raav) serotypes-2 and-5. in vitro and in vivo results demonstrate that this method, which does not require any prepurification step of the cell lysate, can be applied to obtain highly pure raav2 and raav5 stocks. as such,this procedure can be easily transferred in vector cores and also scaled up, allowing the direct comparison o ... | 2002 | 12436964 |
| characterization of the transcription profile of adeno-associated virus type 5 reveals a number of unique features compared to previously characterized adeno-associated viruses. | we report the initial characterization of adeno-associated virus type 5 (aav5) rnas generated following viral infection and the construction of a replicating infectious clone of aav5. while the basic transcription profile of aav5 was similar to that of aav2, there were also significant differences. mapping of the aav5 transcripts demonstrated an efficient transcription initiation site within the aav5 inverted terminal repeat (itr), and mapping of the aav5 intron revealed that it is considerably ... | 2002 | 12438569 |
| a cis-acting element that directs circular adeno-associated virus replication and packaging. | a novel pathway of adeno-associated virus (aav) replication marked by the assembly of circular monomer duplex intermediates (caav) has been recently discovered. in the present report we identify a single ad domain of the inverted terminal repeat as a minimal origin of caav replication. a small internal palindrome (bb'), necessary for optimal rep-inverted terminal repeat interaction, does not contribute to the efficiency of caav replication, while the terminal resolution site is an essential cis- ... | 2002 | 12438604 |
| conjugate-based targeting of recombinant adeno-associated virus type 2 vectors by using avidin-linked ligands. | the development of targeted vectors, capable of tissue-specific transduction, remains one of the important aspects of vector modification for gene therapy applications. recombinant adeno-associated virus type 2 (raav-2)-based vectors are nonpathogenic, have relatively low immunogenicity, and are capable of long-term transgene expression. aav-2 vectors bind primarily to heparan sulfate proteoglycan (hspg), a receptor that is present in many tissues and cell types. because of the widespread expres ... | 2002 | 12438615 |
| a novel gene expression control system and its use in stable, high-titer 293 cell-based adeno-associated virus packaging cell lines. | previous attempts to establish 293cell-based stable and high-titer adeno-associated virus (aav) packaging cell lines were unsuccessful, primarily due to adenovirus e1-activated rep gene expression, which exerts cytostatic and cytotoxic effects on the host cells. control of the two large aav rep proteins (rep78/68) was insufficient to eliminate the adverse effects, because of the leaky expression of the two small rep proteins (rep52/40). however, it was unsuccessful to control rep52/40 gene expre ... | 2002 | 12438627 |
| adeno-associated virus transduction of islets with interleukin-4 results in impaired metabolic function in syngeneic marginal islet mass transplantation. | previous studies suggest that therapeutic expression of interleukin (il)-4 by islet cells improves their efficacy in transplantation models directed at reversing type 1 diabetes. we investigated the effects of introducing il-4 into islets with recombinant adeno-associated virus (raav) on the reversal of hyperglycemia in a syngeneic marginal islet mass transplantation model. c57bl/6 islets were mock-transduced or transduced with raav expressing murine il-4 (raav-il-4) or raav expressing green flu ... | 2002 | 12438968 |
| gene therapy for rheumatoid arthritis. | rheumatoid arthritis (ra) is a severe autoimmune systemic disease. chronic synovial inflammation results in destruction of the joints. no conventional treatment is efficient in ra. gene therapy of ra targets mainly the players of inflammation or articular destruction: tnf-alpha or il-1 blocking agents (such as anti-tnf-alpha monoclonal antibodies, soluble tnf-alpha receptor, type ii soluble receptor of il-1, il-1 receptor antagonist), antiinflammatory cytokines (such as il-4, il-10, il-1), and g ... | 2002 | 12439850 |
| phenotypic rescue after adeno-associated virus-mediated delivery of 4-sulfatase to the retinal pigment epithelium of feline mucopolysaccharidosis vi. | mucopolysaccharidosis vi (mps vi), due to recessively inherited 4-sulfatase (4s) deficiency, results in lysosomal storage of dermatan sulfate in numerous tissues. retinal involvement is limited to the retinal pigment epithelium (rpe). this study aimed to determine whether recombinant adeno-associated virus (aav)-mediated delivery of 4s would reverse the rpe pathology seen in mps vi cats. | 2002 | 12439853 |
| uniform long-term gene expression using adeno-associated virus (aav) by ex vivo recirculation in rat-cardiac isografts. | gene therapy in cardiovascular disease promises to be of great impact. the ideal vector for the therapeutic gene transfection remains to be determined. the aim of the present study was to investigate the efficacy of gene transfer using adeno-associated virus vectors carrying the lacz-reporter gene (aav-lacz) in a previously described coronary recirculation model. | 2002 | 12457311 |
| adeno-associated virus-mediated vascular endothelial growth factor gene therapy in skeletal muscle before transplantation promotes revascularization of regenerating muscle. | successful clinical transplantation of whole skeletal muscles can be limited by impaired muscle revascularization and regeneration. the aim of this study was to enhance the revascularization (and hence speed of regeneration) of transplanted whole muscles by transducing muscles with the vascular endothelial growth factor (vegf) gene before transplantation, using a recombinant adeno-associated virus (raav). the raav encoding vegf and green fluorescent protein (gfp) (raav.vegf.gfp) was injected int ... | 2002 | 12459067 |
| production of clinical-grade recombinant adeno-associated virus vectors. | recombinant adeno-associated viral (raav) vectors are being evaluated in animal models and humans. pre-clinical data demonstrating vector safety, efficiency and efficacy have been used to initiate human clinical trials. the clinical manufacture of raav vectors has supported phase i and phase ii trials, showing that adeno-associated virus serotype 2 vectors are safe when administered to humans. | 2002 | 12459331 |
| dimerizer-regulated gene expression. | control of gene expression using small molecules is a powerful research tool and has clinical utility in the context of regulated gene therapy. use of chemical inducers of dimerization, or dimerizers, for this purpose has several advantages, including tight regulation, modularity to facilitate iterative improvements, and assembly from human proteins to minimize immune responses in clinical applications. recent developments include the use of the rapamycin-based dimerizer system to regulate the e ... | 2002 | 12459338 |
| adeno-associated virus-mediated gene transfer for hemophilia b. | hemophilia is the bleeding diathesis caused by mutations in the gene encoding factor viii (hemophilia a) or factor ix (hemophilia b). currently, the disease is treated by intravenous infusion of the missing purified clotting factor. the goal of gene transfer for treating hemophilia is to achieve sustained expression of factor viii or factor ix at levels high enough to improve the symptoms of the disease. hemophilia has proven to be an attractive model for those interested in gene transfer, and m ... | 2002 | 12463593 |
| immunogenic issues concerning recombinant adeno-associated virus vectors for gene therapy. | 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 ... | 2002 | 12477257 |
| second generation adeno-associated virus type 2-based gene therapy systems with the potential for preferential integration into aavs1. | adeno-associated virus type 2 (aav-2) is a non-pathogenic human parvovirus that is being developed as a gene therapy vector for the treatment of numerous diseases. one property of wild-type aav-2, that is highly desirable in a gene therapy vector, is its ability to preferentially integrate its dna into a 4 kilobase region of human chromosome 19, designated aavs1. one disadvantage of aav-2 is its relatively small packaging capacity, approximately 4.7 kilobases. because of this size limitation, th ... | 2002 | 12109212 |
| recombinant human parvovirus b19 vectors. | in an attempt to exploit the remarkable tissue-tropism of the human parvovirus b19 to target human hematopoietic cells of the erythroid lineage, recombinant human adeno-associated virus 2 genomes were encapsidated in parvovirus b19 capsids. although efficient transduction of primary human hematopoietic cells in the erythroid lineage occurred, a low-level of transgene expression in non-erythroid cells was also detected. these studies suggest that cell surface expression of p antigen, the primary ... | 2002 | 12116848 |
| prevention of chemotherapy-related toxic side effects by infection with adeno-associated virus type 2. | drug resistance and toxic side effects are major limiting factors in the clinical use of antineoplastic chemotherapy. patients with pancreatic cancer generally do not benefit from chemotherapy. the nonpathogenic adeno-associated virus type 2 (aav-2) has been shown to sensitize human tumor cells to gamma irradiation and chemotherapeutic drugs. in the present study, we characterized the therapeutic role of aav-2 infection in combination with 5-fluorouracil (5-fu)-based chemotherapy on pancreatic c ... | 2002 | 12124812 |
| effects of adeno-associated virus-vectored ciliary neurotrophic factor on retinal structure and function in mice with a p216l rds/peripherin mutation. | past studies have shown that acute administration of ciliary neurotrophic factor (cntf) can prolong the survival of retinal photoreceptor cells that have undergone phototoxic injury or that express gene mutations. adenovirus-vectored cntf has also been effective but for all of these treatments, the effect has been transient. on the other hand, adeno-associated virus-vectored minigenes offer considerable promise for long-term survival. the authors sought to provide long-term, cntf-based protectio ... | 2002 | 12126945 |
| leptin-induced leptin resistance reveals separate roles for the anorexic and thermogenic responses in weight maintenance. | the purpose of this study was to determine whether leptin induces leptin resistance by examining the temporal attenuation of the anorexic and energy expenditure responses to leptin. we administered recombinant adeno-associated virus encoding rat leptin cdna or control viral vector into mildly obese rats for 138 d and compared these results with those from pair-fed rats. we measured food consumption, body weight, oxygen consumption, leptin signal transduction, and brown adipose tissue uncoupling ... | 2002 | 12130569 |
| tetracycline-inducible interleukin-10 gene transfer mediated by an adeno-associated virus: application to experimental arthritis. | the adeno-associated viruses (aav) offer new perspectives for cytokine gene transfer in rheumatoid arthritis (ra) because they are nonpathogenic and allow long-term transgene expression in vivo. moreover, the use of a tetracycline-inducible promoter allows regulation of therapeutic gene expression. this study assessed the potential long-term gene regulation of a recombinant aav vector expressing viral interleukin-10 (vil-10) in human rheumatoid synovium and the therapeutic efficiency in a mouse ... | 2002 | 12133271 |
| scalable purification of adeno-associated virus type 2, 4, or 5 using ion-exchange chromatography. | the availability of high-titer, high-purity, adeno-associated virus type 2 (aav2) stocks has dramatically increased our understanding of this virus and its utility as a gene transfer vector. current methods of purification take advantage of the stable interaction of aav2 with heparin sulfate. this affinity chromatography, however, is not useful for purifying aav4 and aav5, because these serotypes lack heparin-binding activity. we have developed simple ion exchange high-performance liquid chromat ... | 2002 | 12133276 |
| [construction, packaging and titration of recombinant adeno-associated virus vectors contaning antitumor genes]. | to construct, package, and titrate vectors that express antitumor genes using adeno-associated virus (aav) containing human alpha-fetoprotein (afp) promoter. | 2002 | 12133507 |
| studies of the mechanism of transactivation of the adeno-associated virus p19 promoter by rep protein. | during adeno-associated virus (aav) type 2 productive infections, the p19 promoter of aav is activated by the aav rep78 and rep68 proteins. rep-induced activation of p19 depends on the presence of one of several redundant rep binding elements (rbes) within the p5 promoter or within the terminal repeats (tr). in the absence of the tr, the p5 rbe and the p19 sp1 site at position -50 are essential for p19 transactivation. to determine how a rep complex bound at p5 induces transcription at p19, we m ... | 2002 | 12134028 |
| immunological aspects of recombinant adeno-associated virus delivery to the mammalian brain. | recombinant adeno-associated viruses (raav) are highly efficient vectors for gene delivery into the central nervous system (cns). however, host inflammatory and immune responses may play a critical role in limiting the use of raav vectors for gene therapy and functional genomic studies in vivo. here, we evaluated the effect of repeated injections of five raav vectors expressing different genetic sequences (coding or noncoding) in a range of combinations into the rat brain. specifically, we wishe ... | 2002 | 12134047 |
| chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac raav gene delivery. | the feasibility of gene therapy for cardiomyopathy, heart failure and other chronic cardiac muscle diseases is so far unproven. here, we developed an in vivo recombinant adeno-associated virus (raav) transcoronary delivery system that allows stable, high efficiency and relatively cardiac-selective gene expression. we used raav to express a pseudophosphorylated mutant of human phospholamban (pln), a key regulator of cardiac sarcoplasmic reticulum (sr) ca(2+) cycling in bio14.6 cardiomyopathic ham ... | 2002 | 12134142 |
| the atomic structure of adeno-associated virus (aav-2), a vector for human gene therapy. | the structure of the adeno-associated virus (aav-2) has been determined to 3-a resolution by x-ray crystallography. aav is being developed as a vector for gene therapy to treat diseases including hemophilia, cancer, and cystic fibrosis. as in the distantly related autonomous parvoviruses, the capsid protein has a beta-barrel fold, but long loops between the beta-strands share little structural homology with other parvoviruses, leading to unique surface features. most prominent are groups of thre ... | 2002 | 12136130 |
| enhancement of green fluorescent protein expression in adeno-associated virus with the woodchuck hepatitis virus post-transcriptional regulatory element. | 2002 | 12136769 | |
| transposase-mediated construction of an integrated adeno-associated virus type 5 helper plasmid. | adeno-associated viruses (aavs) are replication-defective parvoviruses that require helper virusfunctionsfor efficient productive replication. the aavs are currently premier candidates as vectors for human gene therapy applications. in particular; much recent interest has been expressed concerning recombinant aav serotype 5 (raav-5) vectors, as they appear to utilize cellular receptors distinctfrom those of the prototypical aav serotype (aav-2) and have been reported to have transduction propert ... | 2002 | 12139247 |
| interaction of adeno-associated virus rep78 with sv40 t antigen: implications in rep protein expression leading to the inhibition of sv40-mediated cell proliferation. | adeno-associated virus (aav) type 2 is a nonpathogenic human parvovirus that is dependent on a helper virus, usually adenovirus, for its replication. the left half of aav encodes the multifunctional nonstructural proteins required for replication of its dna. here, we present evidence that sv40 provides a helper function for the expression of aav rep protein, as demonstrated by western blot analysis of cell extracts from sv40-transformed human fibroblasts infected with aav. we also show, using a ... | 2002 | 12145545 |
| long-term suppression of weight gain, adiposity, and serum insulin by central leptin gene therapy in prepubertal rats: effects on serum ghrelin and appetite-regulating genes. | intracerebroventricular administration of recombinant adeno-associated virus (raav) encoding the rat leptin gene (raav-lep) to 24-d-old female and male rats suppressed postpubertal weight gain for extended periods by decreasing food consumption and adiposity, as reflected by lowered serum leptin, insulin, and ffa. serum ghrelin levels were increased in young but not older rats. central raav-lep therapy also increased energy expenditure through nonshivering thermogenesis in younger rats as shown ... | 2002 | 12149495 |
| potential new methods for antiepileptic drug delivery. | use of novel drug delivery methods could enhance the efficacy and reduce the toxicity of antiepileptic drugs (aeds). slow-release oral forms of medication or depot drugs such as skin patches might improve compliance and therefore seizure control. in emergency situations, administration via rectal, nasal or buccal mucosa can deliver the drug more quickly than can oral administration. slow-release oral forms and rectal forms of aeds are already approved for use, nasal and buccal administration is ... | 2002 | 12153331 |
| influence of vector dose on factor ix-specific t and b cell responses in muscle-directed gene therapy. | intramuscular injection of an adeno-associated virus (aav) vector has resulted in vector dose-dependent, stable expression of canine factor ix (cf.ix) in hemophilia b dogs with an f.ix missense mutation (herzog et al., nat. med. 1999;5:56-63). the use of a species-specific transgene allowed us to study risks and characteristics of antibody formation against the therapeutic transgene product. we analyzed seven dogs that had been injected at a single time point at multiple intramuscular sites with ... | 2002 | 12162811 |
| a phase ii, double-blind, randomized, placebo-controlled clinical trial of tgaavcf using maxillary sinus delivery in patients with cystic fibrosis with antrostomies. | tgaavcf, an adeno-associated cystic fibrosis transmembrane conductance regulator (cftr) viral vector/gene construct, was administered to 23 patients in a phase ii, double-blind, randomized, placebo-controlled clinical trial. for each patient, a dose of 100,000 replication units of tgaavcf was administered to one maxillary sinus, while the contralateral maxillary sinus received a placebo treatment, thereby establishing an inpatient control. neither the primary efficacy endpoint, defined as the ra ... | 2002 | 12162817 |
| clinical protocol. gene therapy of canavan disease: aav-2 vector for neurosurgical delivery of aspartoacylase gene (aspa) to the human brain. | this clinical protocol describes virus-based gene transfer for canavan disease, a childhood leukodystrophy. canavan disease, also known as van bogaert-bertrand disease, is a monogeneic, autosomal recessive disease in which the gene coding for the enzyme aspartoacylase (aspa) is defective. the lack of functional enzyme leads to an increase in the central nervous system of the substrate molecule, n-acetyl-aspartate (naa), which impairs normal myelination and results in spongiform degeneration of t ... | 2002 | 12162821 |
| generation of neutralizing activity against human immunodeficiency virus type 1 in serum by antibody gene transfer. | although several human immunodeficiency virus (hiv) vaccine approaches have elicited meaningful antigen-specific t-cell responses in animal models, no single vaccine candidate has engendered antibodies that broadly neutralize primary isolates of hiv type 1 (hiv-1). thus, there remains a significant gap in the design of hiv vaccines. to address this issue, we exploited the existence of rare human monoclonal antibodies that have been isolated from hiv-infected individuals. such antibodies neutrali ... | 2002 | 12163597 |
| in vitro and in vivo assessment of the ability of adeno-associated virus-brain-derived neurotrophic factor to enhance spiral ganglion cell survival following ototoxic insult. | auditory dysfunction following ototoxic insult results from loss of cochlear hair cells. secondary degeneration of auditory neurons ensues from withdrawal of neurotrophic support from hair cells and can be prevented with administration of neurotrophins. administration of adeno-associated virus containing the gene for brain-derived neurotrophic factor will promote spiral ganglion neuron survival after the destruction of hair cells. | 2002 | 12172239 |
| infection control for gene therapy: a busy physician's primer. | gene therapy is being studied for the treatment of a wide variety of acquired and inherited disorders. retroviruses, adenoviruses, poxviruses, adeno-associated virus, herpesviruses, and others are being engineered to serve as gene therapy vectors and are being administered to patients in a clinical setting. infection control professionals will be asked to evaluate the use and safety of these agents in their clinics and hospitals. this review summarizes key aspects of the biotechnology and the ve ... | 2002 | 12173136 |
| efficient gene transfer of cd40 ligand into primary b-cll cells using recombinant adeno-associated virus (raav) vectors. | b cells of chronic lymphocytic leukemia (b-cll) are resistant to transduction with most currently available vector systems. using an optimized adenovirus-free packaging system, recombinant adeno-associated virus (raav) vectors coding for the enhanced green fluorescent protein (aav/egfp) and cd40 ligand (aav/cd40l) were packaged and highly purified resulting in genomic titers up to 3 x 10(11)/ml. cells obtained from 24 patients with b-cll were infected with aav/egfp or aav/cd40l at a multiplicity ... | 2002 | 12176885 |
| sustained high-level expression of human factor ix (hfix) after liver-targeted delivery of recombinant adeno-associated virus encoding the hfix gene in rhesus macaques. | the feasibility, safety, and efficacy of liver-directed gene transfer was evaluated in 5 male macaques (aged 2.5 to 6.5 years) by using a recombinant adeno-associated viral (raav) vector (raav-2 cagg-hfix) that had previously mediated persistent therapeutic expression of human factor ix (hfix; 6%-10% of physiologic levels) in murine models. a dose of 4 x 10(12) vector genomes (vgs)/kg of body weight was administered through the hepatic artery or portal vein. persistence of the raav vgs as circul ... | 2002 | 12176886 |
| neuroprotective effects of glial cell line-derived neurotrophic factor mediated by an adeno-associated virus vector in a transgenic animal model of amyotrophic lateral sclerosis. | amyotrophic lateral sclerosis (als) is a relentlessly progressive lethal disease that involves selective annihilation of motoneurons. glial cell line-derived neurotrophic factor (gdnf) is proposed to be a promising therapeutic agent for als and other motor neuron diseases. because adeno-associated virus (aav) has been developed as an attractive gene delivery system with proven safety, we explored the therapeutic efficacy of intramuscular delivery of the gdnf gene mediated by an aav vector (aav-g ... | 2002 | 12177190 |
| recombinant adeno-associated virus-mediated osteoprotegerin gene therapy inhibits wear debris-induced osteolysis. | aseptic loosening of orthopaedic implants secondary to wear debris-induced osteolysis is a serious problem. osteoprotegerin (opg) is a natural decoy protein that inhibits osteoclast activation and bone resorption. this study investigated whether gene therapy using a recombinant adeno-associated viral vector that expresses opg can inhibit wear debris-induced osteolysis. | 2002 | 12177271 |
| glucose-modulated transgene expression via recombinant adeno-associated virus. | the objective of this study was to examine glucose modulated reporter gene expression via recombinant adeno associated viral vectors both in vitro and in vivo. | 2002 | 12180549 |
| sustained hepatic and renal glucose-6-phosphatase expression corrects glycogen storage disease type ia in mice. | deficiency of glucose-6-phosphatase (g6pase), a key enzyme in glucose homeostasis, causes glycogen storage disease type ia (gsd-ia), an autosomal recessive disorder characterized by growth retardation, hypoglycemia, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. g6pase is an endoplasmic reticulum-associated transmembrane protein expressed primarily in the liver and the kidney. therefore, enzyme replacement therapy is not feasible using current strategies, but som ... | 2002 | 12189168 |
| tropism-modified adenoviral and adeno-associated viral vectors for gene therapy. | one of the most rapidly advancing areas of gene therapy is vector development. for the majority of gene therapy procedures, efficient and selective transduction would provide safe and more effective treatments at optimal vector doses. advances in vector targeting strategies have been rapid within the field of dna-based viruses, particularly adenovirus (ad) and more recently adeno-associated virus (aav) based vectors. vector targeting at the level of virus: cell interaction can be achieved using ... | 2002 | 12189716 |
| structural unity among viral origin binding proteins: crystal structure of the nuclease domain of adeno-associated virus rep. | adeno-associated virus (aav), unique among animal viruses in its ability to integrate into a specific chromosomal location, is a promising vector for human gene therapy. aav replication (rep) protein is essential for viral replication and integration, and its amino terminal domain possesses site-specific dna binding and endonuclease activities required for replication initiation and integration. this domain displays a novel endonuclease fold and demonstrates an unexpected structural relationship ... | 2002 | 12191478 |
| novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. | tissues from rhesus monkeys were screened by pcr for the presence of sequences homologous to known adeno-associated virus (aav) serotypes 1-6. dna spanning entire rep-cap orfs from two novel aavs, called aav7 and aav8, were isolated. sequence comparisons among these and previously described aavs revealed the greatest divergence in capsid proteins. aav7 and aav8 were not neutralized by heterologous antisera raised to the other serotypes. neutralizing antibodies to aav7 and aav8 were rare in human ... | 2002 | 12192090 |
| transient platelet interaction induces mcp-1 production by endothelial cells via i kappa b kinase complex activation. | activated platelets alter endothelial chemotactic and adhesive properties. transient interaction of alpha-thrombin-activated platelets with endothelial cells is sufficient to induce secretion of the nf-kappa b-regulated chemokine mcp-1. to evaluate upstream signaling events in platelet-induced nf-kappa b activation, we compared the effect of platelets, il-1 beta or tnf-alpha on i kappa b kinase (ikk) complex activation and i kappa b phosphorylation/proteolysis. kinase assays demonstrated that pl ... | 2002 | 12195705 |
| peripheral but not central leptin prevents the immunosuppression associated with hypoleptinemia in rats. | leptin is a peripheral immunoenhancing reagent that directly activates splenic lymphocytes in mice. we found that a 48 h fast in rats resulted in a decrease in serum leptin that was accompanied by a lower delayed-type hypersensitivity (dth) response. peripheral leptin replacement completely restored this response in fasted animals. we employed a recombinant adeno-associated virus (raav) system to deliver leptin gene directly into rat brain to assess the effect of sustained long-term central expr ... | 2002 | 12208666 |
| light-activated gene transduction enhances adeno-associated virus vector-mediated gene expression in human articular chondrocytes. | to evaluate the effects of ultraviolet (uv) light as an adjuvant for recombinant adeno-associated virus (raav) transduction in human articular chondrocytes. | 2002 | 12209514 |
| adeno-associated virus vector-mediated minidystrophin gene therapy improves dystrophic muscle contractile function in mdx mice. | duchenne muscular dystrophy (dmd) is the most common disabling and lethal genetic muscle disorder, afflicting 1 of every 3500 males. patients with dmd experience progressive muscle degeneration and weakness and succumb to respiratory or cardiac failure by their early twenties. no treatment is currently available for dmd. mutations in the dystrophin gene result in lack of a functional dystrophin protein in striated muscle, which induces instability in the muscle cell membrane leading to persisten ... | 2002 | 12215266 |
| expression of recombinant adeno-associated virus in the brain of rats with a focal embolic stroke via carotid artery. | to study whether recombinant adeno-associated virus (raav) mediated foreign gene, lacz, could pass the blood brain barrier by intra-carotid artery delivery and express in vivo in ischemic brain of the focal embolic stroke rats to investigate a possibility of delivering foreign gene through carotid artery to treat acute ischemic stroke. | 2002 | 12215285 |
| extracellular domain of kinase domain region mediated by adeno-associated virus inhibits growth and angiogenesis of bladder cancer in balb-c mice. | to verify whether the extracellular domain of kinase domain region (kdr) has anti-angiogenesis activity in vivo. | 2002 | 12215294 |
| replication competent helper functions for recombinant aav vector generation. | adeno-associated virus (aav) is a promising gene transfer vector tested in both animal studies and human clinical trials. however, current production methods are generally inefficient and require improvements to meet the increasing clinical need for economical, high titer and high quality raav vectors. the inefficiency of the current systems largely arises from the aav helper function, which contains only the aav coding region but lacks inverted terminal repeats. the terminal repeats were origin ... | 2002 | 12215886 |
| a p5 integration efficiency element mediates rep-dependent integration into aavs1 at chromosome 19. | adeno-associated virus (aav) undergoes site-specific integration into human chromosome 19 through a deletion-substitution mechanism at the well characterized aavs1 site. we have shown previously that a cis element within the left end of the aav genome enhances the efficiency of rep-mediated site-specific integration into chromosome 19 when present in inverted terminal repeat-containing recombinant aav (raav) plasmids. we now demonstrate that a 138-bp cis element, the p5 integration efficiency el ... | 2002 | 12221283 |
| the future of duchenne muscular dystrophy gene therapy: shrinking the dystrophin gene. | duchenne muscular dystrophy is a debilitating muscle-wasting disease caused by mutations in the dystrophin gene - one of the largest genes identified thus far - and which ultimately results in premature death. with no current treatment available, the hopes of many sufferers lie in the establishment of an effective gene therapy. the adeno-associated virus is now emerging as a premium gene transfer vector eliciting minimal immune response from the host and allowing for long-term gene expression. i ... | 2002 | 12222872 |
| oral administration of recombinant adeno-associated virus elicits human immunodeficiency virus-specific immune responses. | oral vaccines can induce both systemic and mucosal immunity. mucosal immunity, especially regional cell-mediated immunity, plays an important role in protecting individuals from infectious diseases such as acquired immunodeficiency syndrome. in this study, a recombinant adeno-associated virus vector expressing human immunodeficiency virus type 1 env gene (aav-hiv) was orally administered to balb/c mice. systemic and regional immunity was induced in the mice. furthermore, the immunization signifi ... | 2002 | 12228012 |