| reporter expression persists 1 year after adeno-associated virus-mediated gene transfer to the optic nerve. | to determine the foci and duration of protein expression following virus-mediated gene transfer to the optic nerve. | 1999 | 10408459 |
| 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 |
| 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 |
| adeno-associated virus vector mediated gene transfer to pancreatic beta cells. | insulin-dependent diabetes mellitus (iddm) or type 1 diabetes is an autoimmune disease that results in destruction of the insulin-producing pancreatic islet beta cells. several factors induce the invasion of immune cells into islets and trigger inflammation. gene therapy approaches targeting the islet cells could be an effective treatment to prevent the onset or reverse type 1 diabetes. allogeneic islet transplantation provides short-term treatment. however, genetically modified islets, which re ... | 2000 | 11021593 |
| adeno-associated virus expresses transgenes in hair follicles and epidermis. | adeno-associated virus (aav) vectors are nonpathogenic, integrating dna vectors capable of transducing dividing and nondividing cells with the potential of long-term expression. evaluating this interesting vector system in the skin for the first time, we found that an aav vector containing the lacz gene (aavlacz) led to the expression of beta-galactosidase for more than 6 weeks following in vivo injection. interestingly, expression was present not only in dividing and postmitotic epidermal kerat ... | 2000 | 10985948 |
| expression of adeno-associated virus integrated transgene within the mammalian vestibular organs. | adeno-associated virus (aav) is a suitable viral vector for transgene expression within the mammalian vestibular organs. | 1998 | 9596192 |
| long-term gene transfer in porcine myocardium after coronary infusion of an adeno-associated virus vector. | viral vector-mediated gene transfer into the heart represents a potentially powerful tool for studying both cardiac physiology as well as gene therapy of cardiac disease. we report here the use of a defective viral vector, which expresses no viral gene products, for gene transfer into the mammalian heart. previous studies have used recombinant viral vectors, which retained viral genes and yielded mostly short-term expression, often with significant inflammation. | 1996 | 8957370 |
| altered beta-adrenergic receptor signaling in heart failure, in vivo gene transfer via adeno and adeno-associated virus. | | 1996 | 8839444 |
| activated forms of vegf-c and vegf-d provide improved vascular function in skeletal muscle. | the therapeutic potential of vascular endothelial growth factor (vegf)-c and vegf-d in skeletal muscle has been of considerable interest as these factors have both angiogenic and lymphangiogenic activities. previous studies have mainly used adenoviral gene delivery for short-term expression of vegf-c and vegf-d in pig, rabbit, and mouse skeletal muscles. here we have used the activated mature forms of vegf-c and vegf-d expressed via recombinant adeno-associated virus (raav), which provides stabl ... | 2009 | 19443835 |
| progress and prospects: techniques for site-directed mutagenesis in animal models. | in the past 2 years, new gene-targeting approaches using adeno-associated virus and designer zinc-finger nucleases have been successfully applied to the production of genetically modified ferrets, pigs, mice and zebrafish. gene targeting using these tools has been combined with somatic cell nuclear transfer and germ cell transplantation to generate gene-targeted animal models. these new technical advances, which do not require the generation of embryonic stem cell-derived chimeras, will greatly ... | 2009 | 19225549 |
| autologous transplantation of epcs encoding fgf1 gene promotes neovascularization in a porcine model of chronic myocardial ischemia. | the functional impairment of endothelial progenitor cells (epcs) constitutes an important barrier for therapeutic angiogenesis. here, we tested the hypotheses that a secreted version of acidic fibroblast growth factor (sp-fgf1) gene transfer may achieve functional improvement of epcs and that autologous transplantation of sp-fgf1-modified epcs can facilitate neovascularization in a porcine model of chronic myocardial ischemia. | 2009 | 19181401 |
| assessment of myocardial blood perfusion improved by cd151 in a pig myocardial infarction model. | to appraise the efficacy of cd151-induced myocardial therapeutic angiogenesis in a pig myocardial infarction model. | 2009 | 19079294 |
| efficient and specific transduction of cochlear supporting cells by adeno-associated virus serotype 5. | congenital deafness, affecting 1 in 1000 neonates, can lead to major problems in speech, cognitive and psychosocial development. congenital deafness is mainly caused by mutations in connexins, hemi-channel proteins forming gap-junctions between supporting cells in the sensory epithelia. we describe a high tropism of aav5 serotype for the supporting cells of the cochlea, both in vitro in postnatal day 4 mouse explants, and in vivo in the adult guinea-pig inner ear, through scala media perfusion. ... | 2008 | 18601973 |
| chondrogenic differentiation of growth factor-stimulated precursor cells in cartilage repair tissue is associated with increased hif-1alpha activity. | to investigate the chondrogenic potential of growth factor-stimulated periosteal cells with respect to the activity of hypoxia-inducible factor 1alpha (hif-1alpha). | 2008 | 18524637 |
| reversal of cardiac dysfunction after long-term expression of serca2a by gene transfer in a pre-clinical model of heart failure. | the aim of this study was to examine the effects of sarcoplasmic reticulum ca(2+) atpase (serca2a) gene transfer in a swine heart failure (hf) model. | 2008 | 18342232 |
| production of cftr-null and cftr-deltaf508 heterozygous pigs by adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer. | progress toward understanding the pathogenesis of cystic fibrosis (cf) and developing effective therapies has been hampered by lack of a relevant animal model. cf mice fail to develop the lung and pancreatic disease that cause most of the morbidity and mortality in patients with cf. pigs may be better animals than mice in which to model human genetic diseases because their anatomy, biochemistry, physiology, size, and genetics are more similar to those of humans. however, to date, gene-targeted m ... | 2008 | 18324337 |
| efficient production of fah-null heterozygote pigs by chimeric adeno-associated virus-mediated gene knockout and somatic cell nuclear transfer. | hereditary tyrosinemia type i (ht1) results in hepatic failure, cirrhosis, and hepatocellular carcinoma (hcc) early in childhood and is caused by a deficiency in the enzyme fumarylacetoacetate hydrolase (fah). in a novel approach we used the chimeric adeno-associated virus dj serotype (aav-dj) and homologous recombination to target and disrupt the porcine fah gene. aav-dj is an artificial chimeric aav vector containing hybrid capsid sequences from three naturally occurring serotypes (aav2, 8, an ... | 2011 | 21674562 |
| cell-based resurfacing of large cartilage defects: long-term evaluation of grafts from autologous transgene-activated periosteal cells in a porcine model of osteoarthritis. | to investigate the potential of transgene-activated periosteal cells for permanently resurfacing large partial-thickness cartilage defects. | 2008 | 18240212 |
| aav serotype 1 mediates more efficient gene transfer to pig myocardium than aav serotype 2 and plasmid. | adeno-associated virus (aav) has many properties of an ideal vector for delivery of therapeutic genes into the myocardium. previous studies in a mouse model of myocardial infarction showed that aav serotype 1 (aav1) is superior to aav serotypes 2-5 to transfer genes into the myocardium by direct injection. since vectors may behave differently in humans and because the human and the pig hearts resemble each other closely, we tested whether aav1 is also superior to aav2 in transferring genes into ... | 2008 | 18044793 |
| cone-specific expression using a human red opsin promoter in recombinant aav. | to determine the feasibility of targeting gene expression specifically to cone photoreceptors using recombinant adeno-associated virus (raav) as the vector. | 2008 | 17905404 |
| comparative biology of raav transduction in ferret, pig and human airway epithelia. | differences between rodent and human airway cell biology have made it difficult to translate recombinant adeno-associated virus (raav)-mediated gene therapies to the lung for cystic fibrosis (cf). as new ferret and pig models for cf become available, knowledge about host cell/vector interactions in these species will become increasingly important for testing potential gene therapies. to this end, we have compared the transduction biology of three raav serotypes (aav1, 2 and 5) in human, ferret, ... | 2007 | 17728794 |
| [expression of hctla4-ig mediated by adeno-associated virus in porcine islets and their biological activity]. | to evaluate the expression of hctla4-ig and their biological function in newborn porcine islets (npis) transfected with aav-hctla4-ig. | 2007 | 17344584 |
| optimizing viral and non-viral gene transfer methods for genetic modification of porcine mesenchymal stem cells. | mesenchymal stem cells (mscs) provide an excellent source of pluripotent progenitor cells for tissue-engineering applications due to their proliferation capacity and differentiation potential. genetic modification of mscs with genes encoding tissue-specific growth factors and cytokines can induce and maintain lineage-specific differentiation. due to anatomical and physiological similarities to humans, porcine research models have been proven valuable for the preclinical testing of tissue enginee ... | 2006 | 17120775 |
| isolation, characterization, gene modification, and nuclear reprogramming of porcine mesenchymal stem cells. | bone marrow mesenchymal stem cells (mscs) are adult pluripotent cells that are considered to be an important resource for human cell-based therapies. understanding the clinical potential of mscs may require their use in preclinical large-animal models, such as pigs. the objectives of the present study were 1) to establish porcine msc (pmsc) cultures; 2) to optimize in vitro pmsc culture conditions, 3) to investigate whether pmscs are amenable to genetic manipulation, and 4) to determine pmsc rep ... | 2006 | 16162872 |
| myocardial gene transfer and long-term expression following intracoronary delivery of adeno-associated virus. | adeno-associated viral vectors (aav) can direct long-term gene expression in post-mitotic cells. previous studies have established that long-term cardiac gene transfer results from intramuscular injection into the heart. cardiac gene transfer after direct intracoronary delivery of aav in vivo, however, has been minimal in degree, and indirect intracoronary delivery, an approach used in an increasing number of studies, appears to be receiving more attention. to determine the utility of indirect i ... | 2005 | 15515115 |
| gene delivery to the mammalian heart using aav vectors. | there are a large number of cardiovascular diseases that could be treated by myocardial gene transfer. these include congestive heart failure, ischemic heart disease, and cardiomyopathy. in addition to its potential for treatment of disease, myocardial gene transfer is useful for the analysis of gene expression and promoter function and for generating animal models of human disease such as pulmonary hypertension. the ideal vector for myocardial gene therapy should give efficient and stable trans ... | 2004 | 14970595 |
| [progress in somatic gene therapy of retinal degeneration in the animal model]. | more than 60 genes responsible for human retinal dystrophies have already been identified. most of them are either expressed in the photoreceptor or in the retinal pigment epithelium (rpe). therefore these cells have become the target of new therapeutical strategies on a molecular level. the most promising approach at present is somatic gene therapy, which has been developed over the last years and the principle has now been established in animal models. for gene therapy of inherited retinal deg ... | 2002 | 12058500 |
| neonatal porcine pancreatic cell clusters as a potential source for transplantation in humans: characterization of proliferation, apoptosis, xenoantigen expression and gene delivery with recombinant aav. | neonatal porcine islets are characterized by reproducible isolation success and high yields, sizable advantages over adult islets. in this work we have analyzed selected phenotypic and functional characteristics of porcine neonatal islets relevant to their possible use for transplant in humans. we show that porcine islet cells proliferate in culture, and synthesize and store islet-specific hormones. proliferating beta cells can be easily identified. implant of cultured neonatal islets in immunod ... | 2002 | 12005100 |
| restriction of equine infectious anemia virus by equine apobec3 cytidine deaminases. | the mammalian apobec3 (a3) proteins comprise a multigene family of cytidine deaminases that act as potent inhibitors of retroviruses and retrotransposons. the a3 locus on the chromosome 28 of the horse genome contains multiple a3 genes: two copies of a3z1, five copies of a3z2, and a single copy of a3z3, indicating a complex evolution of multiple gene duplications. we have cloned and analyzed for expression the different equine a3 genes and examined as well the subcellular distribution of the cor ... | 2009 | 19458006 |
| cd151 gene delivery after myocardial infarction promotes functional neovascularization and activates fak signaling. | our previous studies showed that tetraspanin cd151 promotes neovascularization in rat hindlimb and myocardial ischemia models. this study is to assess whether cd151 induces arteriogenesis and promotes functional neovascularization in a pig myocardial infarction model, and to determine the signaling pathways involved. cd151 cdna and anticd151 sequence were constructed into a recombinant adeno-associated virus (raav) vector. all 26 pigs used either were subjected to coronary artery ligation or did ... | 2009 | 19603100 |
| serca2a gene transfer enhances enos expression and activity in endothelial cells. | congestive heart failure (hf) is associated with impaired endothelium-dependent nitric oxide-mediated vasodilatation. the aim of this study was to examine the effects of sarco/endoplasmic reticulum (er) ca(2+)-atpase 2a (serca2a) gene transfer on endothelial function in a swine hf model. two months after the creation of mitral regurgitation to induce hf, the animals underwent intracoronary injection of adeno-associated virus (aav) carrying serca2a (n = 7) or saline (n = 6). at 4 months, coronary ... | 2010 | 20461063 |
| ultrasound-enhanced drug transport and distribution in the brain. | drug delivery in the brain is limited by slow drug diffusion in the brain tissue. this study tested the hypothesis that ultrasound can safely enhance the permeation of drugs in the brain. in vitro exposure to ultrasound at various frequencies (85 khz, 174 khz, and 1 mhz) enhanced the permeation of tritium-labeled molecules with molecular weight up to 70 kda across porcine brain tissue. a maximum enhancement of 24-fold was observed at 85 khz and 1,200 j/cm(2). in vivo exposure to 1-mhz ultrasound ... | 2010 | 20532711 |
| cotransfection of vascular endothelial growth factor-a and platelet-derived growth factor-b via recombinant adeno-associated virus resolves chronic ischemic malperfusion role of vessel maturation. | we set out to investigate the ability of cardiotropic adeno-associated viral vector (aav2.9 = recombinant adeno-associated virus [raav]) to induce prolonged expression of vascular endothelial growth factor (vegf)-a and platelet-derived growth factor (pdgf)-b in a rabbit hindlimb ischemia model and a pig model of hibernating myocardium. | 2010 | 20650363 |
| transgene expression and effective gene silencing in vagal afferent neurons in vivo using recombinant adeno-associated virus vectors. | vagal afferent fibres innervating thoracic structures such as the respiratory tract and oesophagus are diverse, comprising several subtypes of functionally distinct c-fibres and a-fibres. both morphological and functional studies of these nerve subtypes would be advanced by selective, effective and long-term transduction of vagal afferent neurons with viral vectors. here we addressed the hypothesis that vagal sensory neurons can be transduced with adeno-associated virus (aav) vectors in vivo, in ... | 2010 | 20736420 |
| evaluation and optimization of the administration of recombinant adeno-associated viral vectors (serotypes 2/1, 2/2, 2/rh8, 2/9, and 2/rh10) by convection-enhanced delivery to the striatum. | convection-enhanced delivery (ced) of recombinant adeno-associated virus (raav) vectors is a promising approach for delivery of therapeutic transgenes to the brain. in this study we have systematically examined vector dosing in vivo. infusions of raav serotypes 2/1, 2/2, 2/rh8, 2/9, and 2/rh10 expressing an enhanced green fluorescent protein reporter gene were undertaken into the striatum of rats and pigs using ced. vector distribution, as defined by the volume of distribution and number of tran ... | 2011 | 20836701 |
| high efficiency of brca1 knockout using raav-mediated gene targeting: developing a pig model for breast cancer. | germline inactivating mutations of the breast cancer associated gene 1 (brca1) predispose to breast cancer and account for most cases of familiar breast and/or ovarian cancer. the pig is an excellent model for medical research as well as testing of new methods and drugs for disease prevention and treatment. we have generated cloned brca1 knockout (ko) yucatan miniature piglets by targeting exon 11 using recombinant adeno-associated virus (raav)-mediated gene targeting and somatic cell nuclear tr ... | 2010 | 21181439 |
| chondromodulin 1 stabilizes the chondrocyte phenotype and inhibits endochondral ossification of porcine cartilage repair tissue. | to investigate the effect of chondromodulin 1 on the phenotype of osteochondral progenitor cells in cartilage repair tissue. | 2011 | 21391200 |
| systemic gene delivery in large species for targeting spinal cord, brain, and peripheral tissues for pediatric disorders. | adeno-associated virus type 9 (aav9) is a powerful tool for delivering genes throughout the central nervous system (cns) following intravenous injection. preclinical results in pediatric models of spinal muscular atrophy (sma) and lysosomal storage disorders provide a compelling case for advancing aav9 to the clinic. an important translational step is to demonstrate efficient cns targeting in large animals at various ages. in the present study, we tested systemically injected aav9 in cynomolgus ... | 2011 | 21811247 |
| widespread endogenization of densoviruses and parvoviruses in animal and human genomes. | parvoviruses infect humans and a broad range of animals, from mammals to crustaceans and generally are associated with a variety of acute and chronic diseases. however, many others cause persistent infections and are not known to be associated with any disease. viral persistence is likely related to the ability to integrate into the chromosomal dna and to establish a latent infection. however, there is little evidence for genome integration of parvoviral dna except for adeno-associated virus (aa ... | 2011 | 21795360 |
| cardiac aav9-s100a1 gene therapy rescues post-ischemic heart failure in a preclinical large animal model. | as a prerequisite for clinical application, we determined the long-term therapeutic effectiveness and safety of adeno-associated virus (aav)-s100a1 gene therapy in a preclinical large animal model of heart failure. s100a1, a positive inotropic regulator of myocardial contractility, becomes depleted in failing cardiomyocytes in humans and animals, and myocardial-targeted s100a1 gene transfer rescues cardiac contractile function by restoring sarcoplasmic reticulum calcium (ca(2+)) handling in acut ... | 2011 | 21775667 |
| enhanced sialic acid-dependent endocytosis explains the increased efficiency of infection of airway epithelia by a novel adeno-associated virus. | we previously used directed evolution in human airway epithelia to create adeno-associated virus 2.5t (aav2.5t), a highly infectious chimera of aav2 and aav5 with one point mutation (a581t). we hypothesized that the mechanism for its increased infection may be a higher binding affinity to the surface of airway epithelia than its parent aav5. here, we show that, like aav5, aav2.5t, uses 2,3n-linked sialic acid as its primary receptor; however, aav2.5t binds to the apical surface of human airway e ... | 2011 | 21697483 |
| efficient cochlear gene transfection in guinea-pigs with adeno-associated viral vectors by partial digestion of round window membrane. | the auditory portion of the inner ear, the cochlea, is an ideal organ for local gene transfection owing to its relative isolation. various carriers have been tested for cochlear gene transfection. to date, viral vectors appear to have much higher transfection efficacy than non-viral mechanisms. among these vectors, recombinant adeno-associated virus (raav) vectors have several advantages such as being non-pathogenic and the ability to produce prolonged gene expression in various cell types. howe ... | 2011 | 21697953 |
| sumo1-dependent modulation of serca2a in heart failure. | the calcium-transporting atpase atp2a2, also known as serca2a, is a critical atpase responsible for ca(2+) re-uptake during excitation-contraction coupling. impaired ca(2+) uptake resulting from decreased expression and reduced activity of serca2a is a hallmark of heart failure. accordingly, restoration of serca2a expression by gene transfer has proved to be effective in improving cardiac function in heart-failure patients, as well as in animal models. the small ubiquitin-related modifier (sumo) ... | 2011 | 21900893 |
| aav6.βarkct cardiac gene therapy ameliorates cardiac function and normalizes the catecholaminergic axis in a clinically relevant large animal heart failure model. | aimsg protein-coupled receptor kinase 2 (grk2), which is markedly upregulated in failing human myocardium, has been implicated as a contributing factor or consequence of heart failure (hf). importantly, cardiac-specific grk2 knockout mice have recently proved the pathological nature of grk2 in hf. targeted inhibition of grk2 is possible using a peptide inhibitor known as the βarkct, which has rescued several disparate small animal hf models. this study was designed to evaluate long-term βarkct e ... | 2012 | 22261894 |
| isolation and evaluation of novel adeno-associated virus sequences from porcine tissues. | high antigenic compatibility and low toxicity is associated with xenograft transplantation of porcine tissues in immunodeficient human recipients. we hypothesized that adeno-associated viruses (aavs) of porcine origin could be highly compatible to human tissues and thus of good efficiency and low toxicity for in vivo gene transfer. porcine tissues were screened by pcr for the presence of aav using primers designed to bind conserved regions and amplify variable regions of an alignment of several ... | 2009 | 19626054 |
| [construction of adeno-associated virus vector containing ang-1 gene and its expression in pig mesenchymal stem cells]. | to construct recombinant adeno-associated virus (raav) vector containing angiopoietin-1 (ang-1) gene and to express the ang-1 in targeting cells. | 2009 | 19693974 |
| [arteriogenesis induced by intramyocardial recombinant adeno-associated virus vector encoding human cd151 cdna gene transfer in swines with coronary artery occlusion]. | to investigate the efficacy of cd151 gene delivery in promoting blood perfusion in swines after myocardial infarction. | 2009 | 19927637 |
| adeno-associated viral vector serotypes 1 and 5 targeted to the neonatal rat and pig striatum induce widespread transgene expression in the forebrain. | viral vector-mediated gene transfer has emerged as a powerful means to target transgene expression in the central nervous system. here we characterized the efficacy of serotypes 1 and 5 recombinant adeno-associated virus (raav) vectors encoding green fluorescent protein (gfp) after stereotaxic delivery to the neonatal rat and minipig striatum. the efficiency of gfp expression and the phenotype of gfp-positive cells were assessed within the forebrain at different time points up to 12 months after ... | 2010 | 20025873 |