Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
|---|
| [expression of coagulation factor ix in human cd34 + hematopoietic stem cells by adeno-associated virus 2]. | to investigate the expression of human coagulation factor ix (hfix) gene in human umbilical cord blood (cb) cd34+ cells which was transfected with recombinant adeno-associated virus 2 (raav-2). | 2005 | 16468329 |
| aids vaccine development: perspectives, challenges & hopes. | the worldwide quest for an aids vaccine represents an unprecedented scientific and human challenge for the 21st century. preventive vaccines represent our only long-term hope to stop the epidemic. aids vaccines must be seen as the ultimate prevention tool that will complement the existing prevention strategies in place. the acceleration of vaccine development through the parallel exploration of several scientific approaches and implementation of clinical trials are the best and probably only way ... | 2005 | 15817964 |
| efficacy of an adeno-associated virus 8-pseudotyped vector in glycogen storage disease type ii. | glycogen storage disease type ii (gsd-ii; pompe disease) causes death in infancy from cardiorespiratory failure. the underlying deficiency of acid alpha-glucosidase (gaa; acid maltase) can be corrected by liver-targeted gene therapy in gsd-ii, if secretion of gaa is accompanied by receptor-mediated uptake in cardiac and skeletal muscle. an adeno-associated virus (aav) vector encoding human (h) gaa was pseudotyped as aav8 (aav2/8) and injected intravenously into immunodeficient gsd-ii mice. high ... | 2005 | 15585406 |
| [transfection of human 293 and cd34+ cells with recombinant green fluorescent protein adeno- associated virus]. | to investigate the expressions of recombinant green fluorescent protein (gfp) in 293 cells (human embryonic kidney cells) and cd34(+) cells transfected with adeno-associated virus carrying the gene encoding the recombinant gfp. | 2005 | 15683991 |
| recombinant adeno-associated virus 2-mediated antiangiogenic prevention in a mouse model of intraperitoneal ovarian cancer. | in the present study, we sought to determine the potential of sustained transgene expression by a single i.m. administration of recombinant adeno-associated virus 2 (raav) encoding angiostatin and endostatin in inhibiting i.p. ovarian cancer growth and dissemination in a preclinical mouse model. | 2005 | 15709207 |
| overexpression of soluble trail induces apoptosis in human lung adenocarcinoma and inhibits growth of tumor xenografts in nude mice. | recombinant adeno-associated virus 2/5 (raav2/5), a hybrid raav-2 with aav-5 capsid, seems to be a very efficient delivery vector for the transduction of the lung adenocarcinoma cell line a549. infection of the a549 cell line with a raav2/5 vector encoding the extracellular domain of tumor necrosis factor-related apoptosis-inducing ligand (trail, amino acids 114-281) resulted in secretion of soluble trail (strail) and induction of apoptosis in these cells. raav2/5-strail mediated delivery and st ... | 2005 | 15753363 |
| a dna recombination-based approach to eliminate papillomavirus infection. | at present, no treatments exist that effectively target and eliminate papillomaviruses (pvs) from infected cells or prevent its replication. we are employing a strategy to prevent virus replication in pv-infected cells through the conditional expression of the herpes simplex virus type 1 thymidine kinase (tk) gene. expression of tk in this system is expected to be triggered by a homologous recombination event between the endogenous pv genome and a nonexpressing tk gene cassette. recombination be ... | 2005 | 15756291 |
| recombinant adeno-associated virus type 2-mediated gene transfer into human keratinocytes is influenced by both the ubiquitin/proteasome pathway and epidermal growth factor receptor tyrosine kinase. | efficient gene delivery into keratinocytes is a prerequisite for successful skin gene therapy. vectors based on recombinant adeno-associated virus type 2 (raav-2) offer several promising features that make them attractive for cutaneous applications. however, highly efficient gene delivery may be hampered by different cellular factors, including lack of viral receptors, impairment of cytoplasmic trafficking or limitations in viral second-strand synthesis. this study was undertaken to find factors ... | 2005 | 15776248 |
| adrenomedullin gene delivery alleviates hypertension and its secondary injuries of cardiovascular system. | adrenomedullin (am) is a hypotensive peptide that functions as an important regulator in the cardiovascular and renal systems. the current study explored the potential therapeutic effects of delivering the human am cdna via a novel double-stranded adeno-associated virus vector (dsaav) on hypertension and related complications in spontaneously hypertensive rats (shr). a single dose of dsaav-am vector administered by tail vein injection into adult shr resulted in significant reduction of systolic ... | 2005 | 15812232 |
| adeno-associated virus vectors are able to restore fatty aldehyde dehydrogenase-deficiency. implications for gene therapy in sjogren-larsson syndrome. | sjogren-larsson syndrome (sls) is caused by an autosomal recessive defect in the gene coding for fatty aldehyde dehydrogenase (faldh), an enzyme necessary for the oxidation of long-chain aliphatic aldehydes to fatty acid as one enzyme of the fatty alcohol:nicotinamide-adenine dinucleotide (nad+)-oxidoreductase complex (fao). the impaired activity of faldh leads to the clinical symptom triad of generalized ichthyosis, mental retardation, and spastic diplegia or tetraplegia. treatment options are ... | 2005 | 15834613 |
| identification of an adeno-associated virus rep protein binding site in the adenovirus e2a promoter. | adeno-associated virus (aav) and other parvoviruses inhibit proliferation of nonpermissive cells. the mechanism of this inhibition is not thoroughly understood. to learn how aav interacts with host cells, we investigated aav's interaction with adenovirus (ad), aav's most efficient helper virus. coinfection with ad and aav results in an aav-mediated inhibition of ad5 gene expression and replication. the aav replication proteins (rep) activate and repress gene expression from aav and heterologous ... | 2005 | 15596798 |
| viral transport of dna damage that mimics a stalled replication fork. | adeno-associated virus type 2 (aav2) infection incites cells to arrest with 4n dna content or die if the p53 pathway is defective. this arrest depends on aav2 dna, which is single stranded with inverted terminal repeats that serve as primers during viral dna replication. here, we show that aav2 dna triggers damage signaling that resembles the response to an aberrant cellular dna replication fork. uv treatment of aav2 enhances the g2 arrest by generating intrastrand dna cross-links which persist ... | 2005 | 15596849 |
| adeno-associated virus mediated interferon-gamma inhibits the progression of hepatic fibrosis in vitro and in vivo. | to investigate the effects of adeno-associated virus (aav) mediated expression of human interferon-gamma for gene therapy in experimental hepatic fibrosis in vitro and in vivo. | 2005 | 15996030 |
| nonhuman primate models for diabetic ocular neovascularization using aav2-mediated overexpression of vascular endothelial growth factor. | neovascularization leads to blindness in numerous ocular diseases, including diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, and sickle cell disease. more effective and stable treatments for ocular neovascularization are needed, yet there are major limitations in the present animal models. to develop primate models of diabetic retinopathy and choroidal neovascularization, rhesus monkeys were injected subretinally or intravitreally with an adeno-associated viru ... | 2005 | 15793254 |
| proteasome modulating agents induce raav2-mediated transgene expression in human intestinal epithelial cells. | intestinal gene transfer offers promise as a therapeutic option for treatment of both intestinal and non-intestinal diseases. recombinant adeno-associated virus serotype 2, raav2, based vectors have been utilized to transduce lung epithelial cells in culture and in human subjects. raav2 transduction of intestinal epithelial cells, however, is limited both in culture and in vivo. proteasome-inhibiting agents have recently been shown to enhance raav2-mediated transgene expression in airway epithel ... | 2005 | 15883029 |
| adeno-associated virus vector-mediated delivery of pigment epithelium-derived factor restricts neuroblastoma angiogenesis and growth. | the purpose of this study was to evaluate the ability of adeno-associated virus (aav) vector-mediated delivery of pigment epithelium-derived factor (pedf) to inhibit neuroblastoma (nb) xenograft growth. pigment epithelium-derived factor was chosen for this study because, in addition to being a potent inhibitor of angiogenesis, it is capable of inducing neuronal differentiation. | 2005 | 15868591 |
| stable inhibition of hepatitis b virus proteins by small interfering rna expressed from viral vectors. | there has been much research into the use of rna interference (rnai) for the treatment of human diseases. many viruses, including hepatitis b virus (hbv), are susceptible to inhibition by this mechanism. however, for rnai to be effective therapeutically, a suitable delivery system is required. | 2005 | 15756649 |
| improved neuronal transgene expression from an aav-2 vector with a hybrid cmv enhancer/pdgf-beta promoter. | adeno-associated virus type 2 (aav-2) vectors are highly promising tools for gene therapy of neurological disorders. after accommodating a cellular promoter, aav-2 vectors are able to drive sustained expression of transgene in the brain. this study aimed to develop aav-2 vectors that also facilitate a high level of neuronal expression by enhancing the strength of a neuron-specific promoter, the human platelet-derived growth factor beta-chain (pdgf) promoter. | 2005 | 15756650 |
| adeno-associated virus-vectored gene therapy for retinal disease. | recombinant adeno-associated viral (aav) vectors have become powerful gene delivery tools for the treatment of retinal degeneration in a variety of animal models that mimic corresponding human diseases. aav vectors possess a number of features that render them ideally suited for retinal gene therapy, including a lack of pathogenicity, minimal immunogenicity, and the ability to transduce postmitotic cells in a stable and efficient manner. in the sheltered environment of the retina, aav vectors ar ... | 2005 | 15960597 |
| partial correction of sensitivity to oxidant stress in friedreich ataxia patient fibroblasts by frataxin-encoding adeno-associated virus and lentivirus vectors. | peripheral nervous system (pns) sensory neurons are directly involved in the pathophysiology of a number of debilitating inherited and acquired neurological conditions. the lack of effective treatments for many such conditions provides a strong rationale for exploring novel therapeutic approaches, including gene therapy. friedreich ataxia (frda), a sensory neuropathy, is a progressive neurodegenerative disease associated with a loss of large sensory neurons from the dorsal root ganglia. because ... | 2005 | 16076253 |
| analysis of adeno-associated virus and hpv interaction. | it is slowly becoming accepted that adeno-associated virus (aav) is another significant factor involved in cervical carcinogenesis. however, unlike human papillomavirus (hpv), which is positively associated with cervical cancer, aav is negatively associated with this cancer. this negative association appears to be through a direct and complex bi-directional interaction between aav and hpv. essentially all assays used for studying hpv can be used for studying the aav-hpv interaction. this is beca ... | 2005 | 16350413 |
| intracranial delivery of cln2 reduces brain pathology in a mouse model of classical late infantile neuronal ceroid lipofuscinosis. | classical late infantile neuronal ceroid lipofuscinosis (clincl) is a lysosomal storage disorder caused by mutations in cln2, which encodes lysosomal tripeptidyl peptidase i (tpp1). lack of tpp1 results in accumulation of autofluorescent storage material and curvilinear bodies in cells throughout the cns, leading to progressive neurodegeneration and death typically in childhood. in this study, we injected adeno-associated virus (aav) vectors containing the human cln2 cdna into the brains of cln2 ... | 2006 | 16452657 |
| adeno-associated virus-mediated transduction of vegf165 improves cardiac tissue viability and functional recovery after permanent coronary occlusion in conscious dogs. | we have previously shown that vegf165 gene delivery into ischemic skeletal muscle exerts not only proangiogenic, but also remarkable antiapoptotic and proregenerative activity. the aim of this study was to determine whether recombinant adeno-associated virus (raav)-mediated gene delivery of vegf165 into cardiac muscle, during acute myocardial infarction, exerts a protective effect to promote long-term functional recovery. acute infarction of the anterior lv wall was induced in 12 chronically ins ... | 2006 | 16543500 |
| chimeric herpes simplex virus/adeno-associated virus amplicon vectors. | chimeric or hybrid herpes simplex virus type 1/adeno-associated virus amplicon vectors combine the large transgene capacity of hsv-1 with the potential for site-specific genomic integration and stable transgene expression of aav. these chimeric vectors have been demonstrated to support transgene expression for significantly longer periods than standard hsv-1 amplicons. moreover, hsv/aav hybrid vectors can mediate integration at the aavs1 pre-integration site on human chromosome 19 at a relativel ... | 2006 | 16787183 |
| oncoprotein akt/pkb induces trophic effects in murine models of parkinson's disease. | despite promising preclinical studies, neurotrophic factors have not yet achieved an established role in the treatment of human neurodegenerative diseases. one impediment has been the difficulty in providing these macromolecules in sufficient quantity and duration at affected sites. an alternative approach is to directly activate, by viral vector transduction, intracellular signaling pathways that mediate neurotrophic effects. we have evaluated this approach in dopamine neurons of the substantia ... | 2006 | 17116866 |
| freeze-thaw increases adeno-associated virus transduction of cells. | a combination of gene and cell-based therapies may provide significant advantages over existing treatments in terms of their effectiveness. however, long-term efficient gene delivery has been difficult to achieve in many cell types, including endothelial cells. we developed a freeze-thaw technique which significantly increases the transduction efficiency of recombinant adeno-associated virus vectors in human aortic endothelial cells (23-fold) and in human renal proximal tubular epithelial cells ... | 2006 | 16510845 |
| apobec3a is a potent inhibitor of adeno-associated virus and retrotransposons. | apobec3 proteins constitute a family of cytidine deaminases that provide intracellular resistance to retrovirus replication and transposition of endogenous retroelements. one family member, apobec3a (ha3a), is an orphan, without any known antiviral activity. we show that ha3a is catalytically active and that it, but none of the other family members, potently inhibits replication of the parvovirus adeno-associated virus (aav). ha3a was also a potent inhibitor of the endogenous ltr retroelements, ... | 2006 | 16527742 |
| recombinant aav-mediated hsvtk gene transfer with direct intratumoral injections and tet-on regulation for implanted human breast cancer. | hsvtk/ganciclovir (gcv) gene therapy has been extensively studied in tumors and relies largely on the gene expression of hsvtk. most studies, however, have failed to demonstrate any significant benefit of a controlled gene expression strategy in cancer treatment. the tet-on system is commonly used to regulate gene expression following dox induction. we have evaluated the antitumor effect of hsvtk/ganciclovir gene therapy under tet-on regulation by means of adeno-associated virus-2 (aav-2)-mediat ... | 2006 | 16539746 |
| impact of vegf expression on the physiological characteristics of clonal cell lines. | vascular endothelial growth factor (vegf) plays a crucial role in tumor angiogenesis and growth in most solid neoplasia. | 2006 | 17203773 |
| complete correction of hyperphenylalaninemia following liver-directed, recombinant aav2/8 vector-mediated gene therapy in murine phenylketonuria. | novel recombinant adeno-associated virus vectors pseudotyped with serotype 8 capsid (raav2/8) have recently shown exciting promise as effective liver-directed gene transfer reagents. we have produced a novel liver-specific raav2/8 vector expressing the mouse phenylalanine hydroxylase (pah) cdna and have administered this vector to hyperphenylalaninemic pah-deficient pah(enu2) mice, a model of human phenylketonuria (pku). our hypothesis was that this vector would produce sufficient hepatocyte tra ... | 2006 | 16319949 |
| c-terminal-truncated microdystrophin recruits dystrobrevin and syntrophin to the dystrophin-associated glycoprotein complex and reduces muscular dystrophy in symptomatic utrophin/dystrophin double-knockout mice. | c-terminal-truncated (deltac) microdystrophin is being developed for duchenne muscular dystrophy gene therapy. encouraging results have been achieved in the mdx mouse model. unfortunately, mdx mice do not display the same phenotype as human patients. evaluating deltac microdystrophin in a symptomatic model will be of significant relevance to human trials. utrophin/dystrophin double-knockout (u-dko) mice were developed to model severe dystrophic changes in human patients. in this study we evaluat ... | 2006 | 16563874 |
| prevalence of neutralizing antibodies against adeno-associated virus (aav) types 2, 5, and 6 in cystic fibrosis and normal populations: implications for gene therapy using aav vectors. | adeno-associated virus (aav) vectors are promising candidates for gene therapy directed to the lungs, in particular for treatment of cystic fibrosis (cf). in animal models of lung gene transfer, neutralizing antibodies in serum made in response to vector exposure have been associated with a partial to complete block to repeat transduction by vectors with the same capsid type, thus transduction by aav vectors might be inefficient in humans previously exposed to the same aav type. aav type 2 (aav2 ... | 2006 | 16610931 |
| adeno-associated virus-mediated expression of apolipoprotein (a) kringles suppresses hepatocellular carcinoma growth in mice. | hepatocellular carcinoma (hcc) constitutes more than 90% of all primary liver cancers. hcc is a hypervascular tumor that develops from dedifferentiation of small avascular hcc and is therefore a good target for anti-angiogenic gene therapy. recent studies have identified apolipoprotein(a) [apo(a)] kringles lk68 and lk8 (lks) as having a potential antiangiogenic and anti-tumor activity, and the current study evaluates the therapeutic potential of gene therapy with recombinant adeno-associated vir ... | 2006 | 16628632 |
| adeno-associated virus type 2 increases proteosome-dependent degradation of p21waf1 in a human papillomavirus type 31b-positive cervical carcinoma line. | adeno-associated virus type 2 (aav2) seropositivity is negatively correlated with the development of human papillomavirus (hpv)-associated cervical cancer. we have begun analysis of the molecular mechanisms underlying aav2-mediated onco-suppression through cell cycle regulation in hpv-infected keratinocytes isolated from a low-grade cervical lesion. aav2 superinfection of hpv type 31b (hpv31b)-positive cells at early times postinfection resulted in degradation of the cyclin-dependent kinase (cdk ... | 2006 | 16641284 |
| induction of robust immune responses against human immunodeficiency virus is supported by the inherent tropism of adeno-associated virus type 5 for dendritic cells. | the ability of adeno-associated virus serotype 1 to 8 (aav1 to aav8) vectors expressing the human immunodeficiency virus type 1 (hiv-1) env gp160 (aav-hiv) to induce an immune response was evaluated in balb/c mice. the aav5 vector showed a higher tropism for both mouse and human dendritic cells (dcs) than did the aav2 vector, whereas other aav serotype vectors transduced dcs only poorly. aav1, aav5, aav7, and aav8 were more highly expressed in muscle cells than aav2. an immunogenicity study of a ... | 2006 | 17005662 |
| a helper-dependent capsid-modified adenovirus vector expressing adeno-associated virus rep78 mediates site-specific integration of a 27-kilobase transgene cassette. | random integration of viral gene therapy vectors and subsequent activation or disruption of cellular genes poses safety risks. major efforts in the field are aimed toward targeting vector integration to specific sites in the host genome. the adeno-associated virus (aav) rep78 protein is able to target aav integration to a specific site on human chromosome 19, called aavs1. we studied whether this ability could be harnessed to achieve site-specific integration of a 27-kb transgene cassette into a ... | 2006 | 16987973 |
| [the experimental study of biomimetic artificial cartilage fabrication in vitro and ectopic chondrogenesis in vivo]. | tri-dimensional poly (dl-lactic-co-glycolic acid) (plga) scaffolds were fabricated using a rapid prototyping (rp) technique and the gene of human bone morphogenetic protein 2 (hbmp-2) was transferred into rabbit bone marrow stromal cells (mscs) via recombinant adeno-associated virus vectors (raav-hbmp-2). thirty-two plga scaffolds, size (4 mm x 4 mm x 4 mm), were coated with collagen type i and equally divided into 2 groups. in group a, each scaffold was loaded with 2 x 10(4) hbmp-2 (+) mscs to ... | 2006 | 17002110 |
| short regions of sequence identity between the genomes of human and rodent parvoviruses and their respective hosts occur within host genes for the cytoskeleton, cell adhesion and wnt signalling. | our understanding of the mechanism(s) of pathogenesis and persistence of vertebrate parvoviruses remains incomplete. with the recent availability of the complete genome sequences of human, rat and mouse, and the ability to search these sequences and to locate matches to exact genomic regions, further insight into the interaction of parvoviruses with their human and rodent hosts is possible. to determine the extent and nature of sequence identity between candidate parvoviruses and their respectiv ... | 2006 | 17098972 |
| additional gene therapy with raav-wt-p53 enhanced the efficacy of cisplatin in human bladder cancer cells. | gene therapy is defined as the treatment of an acquired or inherited disease by transfer of genetic material. the most common strategies in gene therapy of bladder cancer are corrective, inductive and cytotoxic gene therapy. mutations in the p53 tumor suppressor gene are the most common molecular genetic abnormalities in bladder cancer and p53 gene transfer in the human bladder cancer cell line by adenoviral or other vectors was demonstrated to be cytotoxic. however, so far there has been no rep ... | 2006 | 17135787 |
| low-dose radiation response of the p21waf1/cip1 gene promoter transduced by adeno-associated virus vector. | in cancer gene therapy, restriction of antitumor transgene expression in a radiation field by use of ionizing radiation-inducible promoters is one of the promising approaches for tumor-specific gene delivery. although tumor suppressor protein p53 is induced by low doses (< 1 gy) of radiation, there have been only a few reports indicating potential utilization of a p53-target gene promoter, such as that of the p21 gene. this is mainly because the transiently transfected promoter of p53-target gen ... | 2006 | 17079872 |
| safety of recombinant adeno-associated virus type 2-rpe65 vector delivered by ocular subretinal injection. | aav2 delivery of the rpe65 gene to the retina of blind rpe65-deficient animals restores vision. this strategy is being considered for human trials in rpe65-associated leber congenital amaurosis (lca), but toxicity and dose efficacy have not been defined. we studied ocular delivery of aav-2/2.rpe65 in rpe65-mutant dogs. there was no systemic toxicity. ocular examinations showed mild or moderate inflammation that resolved over 3 months. retinal histopathology indicated that traumatic lesions from ... | 2006 | 16644289 |
| utility of intraperitoneal administration as a route of aav serotype 5 vector-mediated neonatal gene transfer. | gene transfer into a fetus or neonate can be a fundamental approach for treating genetic diseases, particularly disorders that have irreversible manifestations in adulthood. although the potential utility of this technique has been suggested, the advantages of neonatal gene transfer have not been widely investigated. here, we tested the usefulness of neonatal gene transfer using adeno-associated virus (aav) vectors by comparing the administration routes and vector doses. | 2006 | 16685745 |
| chemotherapeutic agents enhance aav2-mediated gene transfer into breast cancer cells promoting cd40 ligand-based immunotherapy. | supplementing conventional treatment with gene therapy to induce an immune response might be beneficial to cancer patients. in this study, we evaluated the efficiency of transduction of breast cancer cells with recombinant adeno-associated virus (raav) and effects of cytotoxic agents used in chemotherapy. furthermore, the capacity of tumor cells expressing transgenic cd40 ligand (cd40l) to stimulate dendritic cells was measured. | 2006 | 16794829 |
| gene therapy for als: progress and prospects. | amyotrophic lateral sclerosis (als) is a devastating disease for which there are no effective drug treatments to date. recent advances in gene therapy open up the possibility of developing an effective treatment aiming at halting or delaying the degeneration of motor neurons. viral vectors such as lentiviral vectors and adeno-associated virus can transfer genes into many different types of primary neurons from a broad range of species including man and the resulting gene expression is long-term. ... | 2006 | 16806843 |
| serotype-specific detection of adeno-associated virus during laboratory preparation. | adeno-associated virus (aav) is a small single-stranded dna member of the family parvoviradae with at least eight recognized human serotypes, several of which are being studied as candidate vectors for gene therapy. when multiple serotypes are handled in the same laboratory, it is critical to know the serotype of a sample with certainty. here, a rapid and reliable pcr-based method is presented for the identification of serotypes 2, 3b or 6 and for screening for cross contamination. the pcr assay ... | 2006 | 16815560 |
| effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy. | in a clinical study of recombinant adeno-associated virus-2 expressing human factor ix (aav2-fix), we detected 2 impediments to long-term gene transfer. first, preexisting anti-aav neutralizing antibodies (nabs) prevent vector from reaching the target tissue, and second, cd8(+) t-cell responses to hepatocyte-cell surface displayed aav-capsid-terminated fix expression after several weeks. because the vector is incapable of synthesizing viral proteins, a short course of immunosuppression, until aa ... | 2006 | 16868252 |
| gene therapy for hemophilia. | this review will highlight the progress achieved in the past 2 years on using gene therapy to treat hemophilia in animals and humans. | 2006 | 16888433 |
| unique biologic properties of recombinant aav1 transduction in polarized human airway epithelia. | the choice of adeno-associated virus serotypes for clinical applications is influenced by the animal model and model system used to evaluate various serotypes. in the present study, we sought to compare the biologic properties of raav2/1, raav2/2, and raav2/5 transduction in polarized human airway epithelia using viruses purified by a newly developed common column chromatography method. results demonstrated that apical transduction of human airway epithelia with raav2/1 was 100-fold more efficie ... | 2006 | 16899463 |
| re-engineering primary epithelial cells from rhesus monkey parotid glands for use in developing an artificial salivary gland. | there is no satisfactory conventional treatment for patients who experience irreversible salivary gland damage after therapeutic radiation for head and neck cancer or because of sjögren's syndrome. additionally, if most parenchyma is lost, these patients also are not candidates for evolving gene transfer strategies. to help such patients, several years ago we began to develop an artificial salivary gland. in the present study, we used a non-human primate tissue source, parotid glands from rhesus ... | 2006 | 17518661 |
| distribution of aav2-haadc-transduced cells after 3 years in parkinsonian monkeys. | the present report describes for the first time, the stability of recombinant adeno-associated virus serotype 2 (aav2) human aromatic l-amino acid decarboxylase (haadc) gene transfer after 3-year survival time in a non-human primate model of parkinson's disease. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys were treated with six injections of 30 microl/site of aav2-haadc at a concentration of 2 x 10(12) vg/ml into the caudate and putamen. stereological analysis revealed a 46.6% i ... | 2006 | 16407771 |
| a 16bp rep binding element is sufficient for mediating rep-dependent integration into aavs1. | adeno-associated virus (aav) is a non-pathogenic virus and the only known eukaryotic virus capable of targeting human chromosome 19 for integration at a well-characterized aavs1 site. its site-specific integration is mediated by rep68 and rep78, viral proteins that bind to both the viral genome and aavs1 site on ch19 through a specific rep-binding element (rbe) located in both the viral genome and aavs1. there are three rbes in the aav genome: two identical ones in both inverted terminal repeats ... | 2006 | 16516232 |
| development of anticancer gene vaccine interact with human papillomavirus oncoprotein inhibition. | adeno-associated virus (aav) rep 78 protein is known to inhibit the promoter site of several oncogenes and viral genes, including the human papillomavirus (hpv) type 16 e6 transforming genes. the biochemical studies of rep 78 have been reported, but the effects of rep 78 gene-mediated inhibition of hpv 16 e6 promoter activity on the various human cervical carcinoma cells have not been characterized. pegfp-n1 vector, cloned by aav-mediated rep 78, is transfected into cervical carcinoma cells. tra ... | 2006 | 16445644 |
| fatality in mice due to oversaturation of cellular microrna/short hairpin rna pathways. | rna interference (rnai) is a universal and evolutionarily conserved phenomenon of post-transcriptional gene silencing by means of sequence-specific mrna degradation, triggered by small double-stranded rnas. because this mechanism can be efficiently induced in vivo by expressing target-complementary short hairpin rna (shrna) from non-viral and viral vectors, rnai is attractive for functional genomics and human therapeutics. here we systematically investigate the long-term effects of sustained hig ... | 2006 | 16724069 |
| complete prevention of atherosclerosis in apoe-deficient mice by hepatic human apoe gene transfer with adeno-associated virus serotypes 7 and 8. | using intravenous injection of adeno-associated viral (aav) vectors based on novel serotypes 7 and 8, we examined whether liver-specific expression of human apolipoprotein e (apoe) in apoe-deficient mice would completely prevent atherosclerosis after 1 year of sustained expression. | 2006 | 16763161 |
| adeno-associated virus-mediated gene transfer of a secreted form of trail inhibits tumor growth and occurrence in an experimental tumor model. | tumor necrosis factor-related apoptosis-inducing ligand (trail) induces cell death in various tumor cells, but relatively spares normal cells. recombinant adeno-associated virus (raav) vectors have a number of advantages including in vivo long-term gene expression. here, we assessed the biological activity of a novel, secreted form of trail (strail) for cancer gene therapy using a raav2 vector. | 2006 | 16144019 |
| membrane-associated heparan sulfate is not required for raav-2 infection of human respiratory epithelia. | adeno-associated virus type 2 (aav-2) attachment and internalization is thought to be mediated by host cell membrane-associated heparan sulfate proteoglycans (hspg). lack of hspg on the apical membrane of respiratory epithelial cells has been identified as a reason for inefficient raav-2 infection in pulmonary applications in-vivo. the aim of this investigation was to determine the necessity of cell membrane hspg for efficient infection by raav-2. | 2006 | 16630361 |
| safety and efficacy of aav-mediated calpain 3 gene transfer in a mouse model of limb-girdle muscular dystrophy type 2a. | calpainopathy (limb-girdle muscular dystrophy type 2a, lgmd2a) is a recessive muscular disorder caused by deficiency in the calcium-dependent cysteine protease calpain 3. to date, no treatment exists for this disease. we evaluated the potential of recombinant adeno-associated virus (raav) vectors for gene therapy in a murine model for lgmd2a. to drive the expression of calpain 3, we used raav2/1 pseudotyped vectors and muscle-specific promoters to avoid calpain 3 cell toxicity. we report efficie ... | 2006 | 16290124 |
| intracerebral adeno-associated virus-mediated gene transfer in rapidly progressive forms of metachromatic leukodystrophy. | metachromatic leukodystrophy (mld) is a neurodegenerative lysosomal disease caused by a defect of the enzyme arylsulfatase a (arsa) that disrupts the degradation of sulfatides (sulf) in neurons and glial cells. therapy for mld requires active production of arsa in the brain to prevent demyelination and neuronal damage, and efficient delivery of arsa to act faster than disease progression, particularly in the rapidly progressive late infantile form. we used an adeno-associated virus serotype 5 (a ... | 2006 | 16311251 |
| 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 |
| attachment of adeno-associated virus type 3h to fibroblast growth factor receptor 1. | heparan sulfate proteoglycan is thought to act as primary receptor for adeno-associated virus type 2 (aav-2). reported coreceptors include alphavbeta5 integrin, fibroblast growth factor receptor 1 (fgfr-1), and hepatocyte growth factor (c-met). the interaction of aav type 3 (aav-3) with possible cell membrane receptors is incompletely defined. in this study, using assays detecting competition with viral infection, virus binding inhibition assays and dot blotting, we show attachment of aav-3 stra ... | 2006 | 16195782 |
| adeno-associated virus interactions with b23/nucleophosmin: identification of sub-nucleolar virion regions. | adeno-associated virus (aav) is a human parvovirus that normally requires a helper virus such as adenovirus (ad) for replication. the four replication proteins (rep78, 68, 52 and 40) encoded by aav are pleiotropic effectors of virus integration, replication, transcription and virion assembly. using rep68 column chromatography and mass spectrometry, we have identified the nucleolar, b23/nucleophosmin (npm) protein as an rep-interacting partner. rep-npm interactions were verified by co-immunofluor ... | 2007 | 16959286 |
| in vivo post-transcriptional gene silencing of alpha-1 antitrypsin by adeno-associated virus vectors expressing sirna. | alpha-1 antitrypsin (aat) deficiency is one of the most common genetic diseases in north america, with a carrier frequency of approximately 4% in the us population. homozygosity for the most common mutation (glu342lys, pi(*)z) leads to the synthesis of a mutant protein, which accumulates and polymerizes within hepatocytes rather than being efficiently secreted. this lack of secretion causes severe serum deficiency predisposing to chronic lung disease. twelve to fifteen percent of patients with p ... | 2007 | 17592477 |
| production of recombinant adeno-associated viral vectors for in vitro and in vivo use. | adeno-associated virus is a nonpathogenic human virus that has been developed into a gene-delivery vector due to its high efficiency of infection in many different cell types and its ability to persist and lead to long-term gene expression. the vector is also a valuable tool in molecular biology experiments. this unit describes efficient methods to generate high-titer, research-grade, adenovirus-free, recombinant single-stranded and self-complementary adeno-associated virus in various serotypes, ... | 2007 | 18265393 |
| intraperitoneal gene therapy by raav provides long-term survival against epithelial ovarian cancer independently of survivin pathway. | epithelial ovarian carcinoma is the leading cause of death from gynecological malignancies. owing to the lack of an effective screening method, insidious onset, and non-specific symptoms, a majority of women present with advanced stage disease. despite improvements from cytoreductive surgery and chemotherapy, recurrent disease remains a formidable challenge. in the present study, we demonstrate for the first time that stable intra-abdominal genetic transfer of endostatin and angiostatin (e+a) by ... | 2007 | 16943851 |
| pre-existing aav capsid-specific cd8+ t cells are unable to eliminate aav-transduced hepatocytes. | the goal of these studies was to test whether adeno-associated virus (aav) capsid-specific cd8(+) t cells cause loss of hepatic aav-mediated gene expression in experimental animals. mice immunized with adenoviral vectors expressing aav capsid or with aav vectors developed cd8(+) t cells in blood, lymphatic tissues, and liver to epitopes shared between aav2 and aav8, and serotype-specific neutralizing antibodies. at the height of the t cells' effector phase, mice were infused with a heterologous ... | 2007 | 17245353 |
| increased complexity of wild-type adeno-associated virus-chromosomal junctions as determined by analysis of unselected cellular genomes. | adeno-associated virus (aav) undergoes preferential rep-mediated integration into the aavs1 region of human chromosome 19 during latent infection, at least in highly-selected cell cultures. however, integration at the level of the whole eukaryotic genome in unselected cells has not yet been monitored for aav as it has been for retro- and lentiviruses. here we have used ligation-mediated pcr (lmpcr) to monitor the formation of aav-chromosome junctions within unselected genomic dna after infection ... | 2007 | 17485532 |
| quiescent subpopulations of human cd34-positive hematopoietic stem cells are preferred targets for stable recombinant adeno-associated virus type 2 transduction. | we have previously demonstrated recombinant adeno-associated viral (raav) transduction of human cd34(+) hematopoietic stem cells (hscs) capable of serial engraftment in vivo. here we evaluated the capacity of raav2 to mediate gene transfer into nondividing, quiescent, primitive cd34(+) cells subdivided on the basis of metabolic, mitotic, and phenotypic properties. results revealed that cd34(+)cd38() marrow cells are the most quiescent, exist primarily in g(0) at isolation and are the only popula ... | 2007 | 17638572 |
| therapeutic approaches for prion disorders. | prion diseases are lethal for both humans and animals, and affected individuals die after several months following a rapid disease progression. although researchers have attempted for decades to develop effective therapeutics for the therapy of human prion disorders, until now no efficient drug has been available on the market for transmissible spongiform encephalopathy (tse) treatment or cure. approximately 200 patients worldwide have died or suffer from variant creutzfeldt-jakob disease (cjd). ... | 2007 | 17678425 |
| raav-mediated nigral human parkin over-expression partially ameliorates motor deficits via enhanced dopamine neurotransmission in a rat model of parkinson's disease. | we hypothesized that over-expressing the e3 ligase, parkin, whose functional loss leads to parkinson's disease, in the nigrostriatal tract might be protective in the unilateral 6-hydroxydopamine (6-ohda) rat lesion model. recombinant adeno-associated virus (raav) encoding human parkin or green fluorescent protein (gfp) was injected into the rat substantia nigra 6 weeks prior to a four-site striatal 6-ohda lesion. vector-mediated parkin over-expression significantly ameliorated motor deficits as ... | 2007 | 17678648 |
| vaccines based on novel adeno-associated virus vectors elicit aberrant cd8+ t-cell responses in mice. | we recently discovered an expanded family of adeno-associated viruses (aavs) that show promise as improved gene therapy vectors. in this study we evaluated the potential of vectors based on several of these novel aavs as vaccine carriers for human immunodeficiency virus type 1 gag. studies with mice indicated that vectors based on aav type 7 (aav7), aav8, and aav9 demonstrate improved immunogenicity in terms of gag cd8(+) t-cell and gag antibody responses. the quality of these antigen-specific r ... | 2007 | 17715240 |
| knock-in of oncogenic kras does not transform mouse somatic cells but triggers a transcriptional response that classifies human cancers. | kras mutations are present at a high frequency in human cancers. the development of therapies targeting mutated kras requires cellular and animal preclinical models. we exploited adeno-associated virus-mediated homologous recombination to insert the kras g12d allele in the genome of mouse somatic cells. heterozygous mutant cells displayed a constitutively active kras protein, marked morphologic changes, increased proliferation and motility but were not transformed. on the contrary, mouse cells i ... | 2007 | 17875685 |
| repeated aerosolized aav-cftr for treatment of cystic fibrosis: a randomized placebo-controlled phase 2b trial. | previous studies have demonstrated that delivery of a recombinant adeno-associated virus (aav) vector encoding the complete human cystic fibrosis transmembrane regulator (cftr) cdna (tgaavcf) to the nose, sinus, and lungs of subjects with cystic fibrosis (cf) was safe and well tolerated. in a small randomized, double-blind study of three doses of aerosolized tgaavcf or placebo at 30-day intervals, encouraging but non-significant trends in pulmonary function and induced sputum interleukin 8 (il-8 ... | 2007 | 17685853 |
| gender differences in serotype 2 adeno-associated virus biodistribution after administration to rodent salivary glands. | salivary glands (sgs) have proven useful targets for clinical applications of gene therapeutics. in this toxicology and biodistribution study, which conforms to u.s. food and drug administration good laboratory practice regulations, four doses (10(7)-10(10) particles) of a serotype 2 adeno-associated viral (aav2) vector encoding human erythropoietin were directly administered to the right submandibular gland of male and female balb/c mice (n = 21 per gender dose group). control-treated (saline a ... | 2007 | 17939749 |
| therapeutic silencing of mutant huntingtin with sirna attenuates striatal and cortical neuropathology and behavioral deficits. | huntington's disease (hd) is a neurodegenerative disorder caused by expansion of a cag repeat in the huntingtin (htt) gene. hd is autosomal dominant and, in theory, amenable to therapeutic rna silencing. we introduced cholesterol-conjugated small interfering rna duplexes (cc-sirna) targeting human htt mrna (sirna-htt) into mouse striata that also received adeno-associated virus containing either expanded (100 cag) or wild-type (18 cag) htt cdna encoding huntingtin (htt) 1-400. adeno-associated v ... | 2007 | 17940007 |
| intraparenchymal spinal cord delivery of adeno-associated virus igf-1 is protective in the sod1g93a model of als. | the potent neuroprotective activities of neurotrophic factors, including insulin-like growth factor 1 (igf-1), make them promising candidates for treatment of amyotrophic lateral sclerosis (als). in an effort to maximize rate of motor neuron transduction, achieve high levels of spinal igf-1 and thus enhance therapeutic benefit, we injected an adeno-associated virus 2 (aav2)-based vector encoding human igf-1 (cere-130) into lumbar spinal cord parenchyma of sod1(g93a) mice. we observed robust and ... | 2007 | 17963733 |
| immune responses to adenovirus and adeno-associated vectors used for gene therapy of brain diseases: the role of immunological synapses in understanding the cell biology of neuroimmune interactions. | researchers have conducted numerous pre-clinical and clinical gene transfer studies using recombinant viral vectors derived from a wide range of pathogenic viruses such as adenovirus, adeno-associated virus, and lentivirus. as viral vectors are derived from pathogenic viruses, they have an inherent ability to induce a vector specific immune response when used in vivo. the role of the immune response against the viral vector has been implicated in the inconsistent and unpredictable translation of ... | 2007 | 17979681 |
| calculating expected lung deposition of aerosolized administration of aav vector in human clinical studies. | cystic fibrosis is an autosomal recessive disease affecting approximately 1 in 2500 live births. introducing the cdna that codes for normal cystic fibrosis transmembrane conductance regulator (cftr) to the small airways of the lung could result in restoring the cftr function. a number of vectors for lung gene therapy have been tried and adeno-associated virus (aav) vectors offer promise. the vector is delivered to the lung using a breath-actuated jet nebulizer. the purpose of this project was to ... | 2007 | 17154340 |
| phenotypic correction of alpha-sarcoglycan deficiency by intra-arterial injection of a muscle-specific serotype 1 raav vector. | alpha-sarcoglycanopathy (limb-girdle muscular dystrophy type 2d, lgmd2d) is a recessive muscular disorder caused by deficiency in alpha-sarcoglycan, a transmembrane protein part of the dystrophin-associated complex. to date, no treatment exists for this disease. we constructed recombinant pseudotype-1 adeno-associated virus (raav) vectors expressing the human alpha-sarcoglycan cdna from a ubiquitous or a muscle-specific promoter. evidence of specific immune response leading to disappearance of t ... | 2007 | 17164775 |
| phosphorylation-dependent degradation of transgenic creb protein initiated by heterodimerization. | the transcription factor creb (cyclic amp response element binding protein) is implicated in diverse brain functions and represents a prospective target in gene therapy for human disorders. however, the transgenic expression and stability of exogenously expressed creb within the cell remains poorly characterized. here we found that transient expression of a creb dominant interfering mutant a-creb or the inducible camp early repressor, icer, led to the dramatic decrease of exogenously co-expresse ... | 2007 | 17169345 |
| sumf1 enhances sulfatase activities in vivo in five sulfatase deficiencies. | sulfatases are enzymes that hydrolyse a diverse range of sulfate esters. deficiency of lysosomal sulfatases leads to human diseases characterized by the accumulation of either gags (glycosaminoglycans) or sulfolipids. the catalytic activity of sulfatases resides in a unique formylglycine residue in their active site generated by the post-translational modification of a highly conserved cysteine residue. this modification is performed by sumf1 (sulfatase-modifying factor 1), which is an essential ... | 2007 | 17206939 |
| [gfp gene transfection of dendritic cells mediated by recombinated adeno-associated virus]. | to investigate the transfection condition of type 2 recombinant adeno-associated virus ( raav2) in human dendritic cells(dcs) which were induced from the bone marrow cd34+ hematopoietic stem /progenitor cells. | 2007 | 18007063 |
| gangliosides, ab1 and ab2 antibodies iii. the idiotype of anti-ganglioside mab p3 is immunogenic in a t cell-dependent manner. | p3 mab is an igm monoclonal antibody specific for n-glycolyl-containing gangliosides. the immunogenicity of the p3 idiotype has been previously described by immunizing syngeneic balb/c mice with the purified murine igm or the mouse-human chimeric igg antibody. in the present work we study the antibody response against the idiotype of p3 mab through immunization with dna. we used small immune proteins (sip) consisting on the idiotype in the scfv format, covalently linked to gamma1ch3, the self-di ... | 2007 | 17316805 |
| self-complementary recombinant adeno-associated viral vectors: packaging capacity and the role of rep proteins in vector purity. | self-complementary adeno-associated viral (scaav) vectors bypass the requirement for viral second-strand dna synthesis, but the packaging capacity of these vectors ( approximately 2.4 kb) is significantly smaller than that of conventional aav vectors ( approximately 4.8 kb). we constructed human recombinant green fluorescent protein (hrgfp) expression cassettes ranging from 2.3 to 4.1 kb. each vector was biologically active, but the transduction efficiency of vectors containing <3.3-kb genomes w ... | 2007 | 17328683 |
| striatal delivery of cere-120, an aav2 vector encoding human neurturin, enhances activity of the dopaminergic nigrostriatal system in aged monkeys. | neurturin (ntn) is a potent survival factor for midbrain dopaminergic neurons. cere-120, an adeno-associated virus type 2 (aav2) vector encoding human ntn (aav2-ntn), is currently being developed as a potential therapy for parkinson's disease. this study examined the bioactivity and safety/tolerability of aav2-ntn in the aged monkey model of nigrostriatal dopamine insufficiency. aged rhesus monkeys received unilateral injections of aav2-ntn into the caudate and putamen, with each animal therefor ... | 2007 | 17443702 |
| papillary thyroid carcinoma with lymph node metastases. | papillary thyroid cancer (ptc) is the most frequently occurring human thyroid cancer with good prognosis following appropriate treatment. lymph node (ln) metastases are the main way through which ptc spread cancer cells. the mechanisms underlying ptc with local invasion, ln metastases and distant metastases are not well investigated. tumor secrete cytokines, such as vascular endothelial growth factor (vegf)-c and -d bind to vegf receptors on lymphatic endothelial cells and induce proliferation ( ... | 2007 | 17454149 |
| systemic cancer gene therapy using adeno-associated virus type 1 vector expressing mda-7/il24. | melanoma differentiation-associated gene-7/interleukin-24 (mda-7/il24), selectively induces apoptosis in cancer cells without harming normal cells. it also exerts immunomodulatory and antiangiogenic effects, as well as potent antitumor bystander effects, making it an ideal candidate for a new anticancer gene therapy. here, we examined the feasibility of adeno-associated virus type 1 (aav1) vector-mediated systemic gene therapy using mda-7/il24. in vitro studies showed that medium conditioned by ... | 2007 | 17551500 |
| gene therapy: the first two decades and the current state-of-the-art. | the concept of gene therapy was envisioned soon after the emergence of restriction endonucleases and subcloning of mammalian genes in phage and plasmids. over the ensuing decades, vectors were developed, including nonviral methods, integrating virus vectors (gammaretrovirus and lentivirus), and non-integrating virus vectors (adenovirus, adeno-associated virus, and herpes simplex virus vectors). preclinical data demonstrated potential efficacy in a broad range of animal models of human diseases, ... | 2007 | 17577203 |
| adeno-associated virus 2-mediated gene transfer: role of a cellular serine/threonine protein phosphatase in augmenting transduction efficiency. | we have documented that a cellular chaperone protein, fkbp52, when phosphorylated at tyrosine and/or serine/threonine (ser/thr) residues, interacts with the d-sequence in the inverted terminal repeats of the adeno-associated virus 2 (aav) genome, inhibits the viral second-strand dna synthesis, and leads to inefficient transgene expression from recombinant aav vectors in certain cell types. we have also demonstrated that fkbp52 is dephosphorylated at tyrosine residues by t-cell protein tyrosine p ... | 2007 | 17122803 |
| 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 |
| chemical rescue of deltaf508-cftr mimics genetic repair in cystic fibrosis bronchial epithelial cells. | in a previous study of sodium 4-phenylbutyrate (4-pba)-responsive proteins in cystic fibrosis (cf) ib3-1 bronchial epithelial cells, we identified 85 differentially expressed high abundance proteins from whole cellular lysate (singh, o. v., vij, n., mogayzel, p. j., jr., jozwik, c., pollard, h. b., and zeitlin, p. l. (2006) pharmacoproteomics of 4-phenylbutyrate-treated ib3-1 cystic fibrosis bronchial epithelial cells. j. proteome res. 5, 562-571). in the present work we hypothesize that a subse ... | 2008 | 18285607 |
| anti-idiotypic response in mice expressing human autoantibodies. | celiac disease is an autoimmune illness characterized by intestinal mucosal injury and malabsorption precipitated by dietary exposure to gluten of some cereals. the immune response is based on both cellular and humoral components, although the former seem to be more important in the pathogenesis. the autoantibody response is directed at the enzyme tissue transglutaminase, ttg or tg2, which possibly play a role in the onset of the disease. in this study we sought to develop an animal model in whi ... | 2008 | 17996305 |
| targeted integration of functional human atm cdna into genome mediated by hsv/aav hybrid amplicon vector. | ataxia-telangiectasia (a-t) is an autosomal recessive disorder characterized by neurodegeneration, immunodeficiency, cancer predisposition, genome instability, and sensitivity to ionizing radiation (ir). we have previously shown that a herpes simplex virus type 1 (hsv-1) amplicon vector carrying the human ataxia-telangiectasia mutated (atm) complementary dna (cdna) is able to correct aspects of the cellular phenotype of human a-t cells in culture, and is also able to transfer the atm cdna to the ... | 2008 | 17998902 |
| engineering adeno-associated virus 2 vectors for targeted gene delivery to atherosclerotic lesions. | targeted delivery of biological agents to atherosclerotic plaques may provide a novel treatment and/or useful tool for imaging of atherosclerosis in vivo. however, there are no known viral vectors that possess the desired tropism. two plaque-targeting peptides, capgpsksc (cap) and cnhrymqmc (cnh) were inserted into the capsid of adeno-associated virus 2 (aav2) to assess vector retargeting. aav2-cnh produced significantly higher levels of transduction than unmodified aav2 in human, murine and rat ... | 2008 | 18004401 |
| human apolipoprotein e expression from mouse skeletal muscle by electrotransfer of nonviral dna (plasmid) and pseudotyped recombinant adeno-associated virus (aav2/7). | plasma apolipoprotein e (apoe) has multiple atheroprotective actions. however, although liver-directed adenoviral gene transfer of apoe reverses hypercholesterolemia and inhibits atherogenesis in apoe-deficient (apoe(-/-)) mice, safety considerations have revived interest in nonviral dna (plasmid) and nonpathogenic adeno-associated viral (aav) vectors. here, we assess the effectiveness of these two delivery vehicles by minimally invasive intramuscular injection. first, we constructed aav2-based ... | 2008 | 18578629 |
| the effect of surface demineralization of cortical bone allograft on the properties of recombinant adeno-associated virus coatings. | freeze-dried recombinant adeno-associated virus (raav) coated structural allografts have emerged as an approach to engender necrotic cortical bone with host factors that will persist for weeks following surgery to facilitate revascularization, osteointegration, and remodeling. however, one major limitation is the nonporous cortical surface that prohibits uniform distribution of the raav coating prior to freeze-drying. to overcome this we have developed a demineralization method to increase surfa ... | 2008 | 18590929 |
| robust, persistent transgene expression in human embryonic stem cells is achieved with aavs1-targeted integration. | silencing and variegated transgene expression are poorly understood problems that can interfere with gene function studies in human embryonic stem cells (hescs). we show that transgene expression (enhanced green fluorescent protein [egfp]) from random integration sites in hescs is affected by variegation and silencing, with only half of hescs expressing the transgene, which is gradually lost after withdrawal of selection and differentiation. we tested the hypothesis that a transgene integrated i ... | 2008 | 18024421 |
| inherited diseases of photoreceptors and prospects for gene therapy. | the photoreceptor cells of the retina are subject to a wide range of genetic diseases. this review summarizes current knowledge regarding an important group of retinal diseases caused by mutations in photoreceptor-enriched genes. in addition, progress toward treatment of a variety of these diseases in animal models via adeno-associated virus gene therapy is described. although no human trials have yet been initiated to treat diseases caused by mutations in photoreceptor-enriched genes, there is ... | 2008 | 18303969 |
| human gene targeting favors insertions over deletions. | gene targeting is a powerful technique for manipulating the human genome, but few studies have directly compared the targeting frequencies of various types of vector constructs. here we show that similar targeting constructs are able to insert nucleotides at the homologous chromosomal target locus more efficiently than they can delete nucleotides, and combination insertion/deletion vectors appear to target at intermediate frequencies. this holds true for deletions ranging from 1 to 334 bp and in ... | 2008 | 18680404 |
| 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 |
| adeno-associated virus type 12 (aav12): a novel aav serotype with sialic acid- and heparan sulfate proteoglycan-independent transduction activity. | recombinant adeno-associated virus (raav) is a promising vector for gene therapy. recent isolations of novel aav serotypes have led to significant advances by broadening the tropism and increasing the efficiency of gene transfer to the desired target cell. however, a major concern that remains is the strong preexisting immune responses to several vectors. in this paper, we describe the isolation and characterization of aav12, an aav serotype with unique biological and immunological properties. i ... | 2008 | 18045941 |