Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
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| gene therapy in ophthalmology: validation on cultured retinal cells and explants from postmortem human eyes. | gene therapy studies in primates can provide important information regarding vector tropism, specific cellular expression, biodistribution, and safety prior to clinical trials. in this study, we report the assessment of transduction efficiency of recombinant adeno-associated virus (raav) vectors using human postmortem retina. transductions were performed using two in vitro models prepared from human tissue: dissociated cell cultures and retinal explants. these models were used to assess cellular ... | 2011 | 21142470 |
| characterization of anti-hiv activity mediated by r88-apobec3g mutant fusion proteins in cd4(+) t cells, peripheral blood mononuclear cells, and macrophages. | abstract in this study, we characterized the anti-hiv activities of various r88-apobec3g (r88-a3g) mutant fusion proteins in which each a3g mutant was fused with a virus-targeting polypeptide (r14-88, hereafter named r88) derived from hiv-1 vpr. our results show that the introduction of the deaminase-defective mutant e259q into r88-a3g did not affect the virion incorporation of this mutant but blocked the protein's ability to inhibit hiv-1 infection. our data also reveal that the antiviral effec ... | 2011 | 21182427 |
| an adeno-associated virus vector efficiently and specifically transduces mouse skeletal muscle. | expression of a therapeutic gene in the skeletal muscle is a practical strategy to compensate a patients' insufficient circulating factor. its clinical application requires a muscle-targeting vector capable of inducing a continuous high-level transgene expression. we modified an adeno-associated virus serotype 2 (aav2) vector expressing luciferase from the mouse muscle creatine kinase gene promoter-enhancer (ckm). first, aavs1 insulator was inserted into the vector genome for transcriptional enh ... | 2011 | 21197588 |
| labeling and tracking human amniotic epithelial cells with green fluorescent protein in an adeno-associated virus vector. | human amniotic epithelial cells (haecs) are a recently identified type of stem cell. thanks to their ready availability and the lower risk of teratoma formation, haecs have been studied and tested for a variety of human disease treatments and tissue reconstruction efforts. this aim of this study was to establish a stable tracking system to further monitor haecs in vivo after transplantation. haecs were isolated from the placentas of patients who visited the hunan province maternity and child car ... | 2011 | 21225467 |
| systemic elimination of de novo capsid protein synthesis from replication-competent aav contamination in the liver. | the capsid protein synthesis in targeted tissues resulting from residual contaminating replication-competent adeno-associated virus particles (rcaav) remains a concern for hazardous immune responses that shut down the factor ix expression in the hemophilia b clinical trial. to systematically reduce/eliminate the effects of potential contaminating rcaav particles, we designed a novel adeno-associated virus (aav) helper (ph22mir) with a microrna binding cassette containing multiple copies of liver ... | 2011 | 21244243 |
| functional characterization of 58-kilodalton inhibitor of protein kinase in protecting against diabetic retinopathy via the endoplasmic reticulum stress pathway. | 58-kilodalton inhibitor of protein kinase (p58(ipk)) plays an important role in preventing endoplasmic reticulum (er) stress. it is an interferon-induced kinase that targets the eukaryotic translation initiation factor eukaryotic initiation factor 2 alpha. the aim of this study was to determine the roles of p58(ipk) in protecting against diabetic retinopathy (dr) by inhibiting er stress-signaling mediators. | 2011 | 21245960 |
| effects of adeno-associated virus-2-mediated human bmp-7 gene transfection on the phenotype of nucleus pulposus cells. | bone morphogenetic protein-7 (bmp-7) was found to stimulate the synthesis of proteoglycans (pgs) and collagen type ii. to increase the biological function of the nucleus pulposus (np) cells, the ad-hbmp-7 vector was also successfully constructed and transfected np cells. however, the disadvantages of adenovirus limit the usefulness of the ad-hbmp7 vector for clinical application. the raav2 vector has empirical advantages, especially for clinical use, to transfer exogenous genes into cells. the p ... | 2011 | 21246612 |
| cystic fibrosis transmembrane conductance regulator with a shortened r domain rescues the intestinal phenotype of cftr-/- mice. | gene transfer could provide a novel therapeutic approach for cystic fibrosis (cf), and adeno-associated virus (aav) is a promising vector. however, the packaging capacity of aav limits inclusion of the full-length cystic fibrosis transmembrane conductance regulator (cftr) cdna together with other regulatory and structural elements. to overcome aav size constraints, we recently developed a shortened cftr missing the n-terminal portion of the r domain (residues 708-759, cftr?r) and found that it r ... | 2011 | 21285372 |
| synergistic antitumor effect of aav-mediated trail expression combined with cisplatin on head and neck squamous cell carcinoma. | 2011 | 21291526 | |
| safe and effective gene transfer by adeno-associated virus of neonatal thymus-derived mesenchymal stromal cells. | recently, human neonatal thymus-derived mesenchymal stromal cells (ntmscs) have been recognized as a promising mesenchymal stem cell source for combined cell and gene therapy. while efficient gene transfer is crucial for optimizing therapeutic efficacy, almost no studies have yet reported on the characteristics of ntmsc in terms of genetic modification. the present study investigates and realizes the potential of self-complementary adeno-associated viruses (scaavs) as an effective transduction t ... | 2011 | 21310455 |
| [post-translational ligation and function of dual-vector transferred split cftr gene]. | the mutation of cystic fibrosis transmembrane conductance regulator (cftr) gene leads to an autosomal recessive genetic disorder cystic fibrosis (cf). the gene therapy for cf using adeno-associated virus (aav) vectors delivering cftr gene is restricted by the contents limitation of aav vectors. in this study the split cftr genes severed at its regulatory domain were delivered by a dual-vector system with an intein-mediated protein trans-splicing as a technique to investigate the post-translation ... | 2010 | 21351451 |
| [post-translational ligation of split cftr severed before tmd2 and its chloride channel function]. | mutations of cystic fibrosis transmembrane conductance regulator (cftr) gene leads to cystic fibrosis, an autosomal recessive genetic disorder affecting a number of organs including the lung airways, pancreas and sweat glands. in order to investigate the post-translational ligation of cftr with reconstructed functional chloride ion channel and the split ssp dnab intein-mediated protein trans-splicing was explored to co-deliver cftr gene into eukaryotic cells with two vectors. the human cftr cdna ... | 2010 | 21387835 |
| generation of recombinant adeno-associated virus. | adeno-associated virus (aav) was discovered about 30 yr ago as a contaminant of adenovirus preparations. since its discovery, researchers have described many unique characteristics of aav biology that have made it attractive as a potential vector for gene therapy. for example, aav is not pathogenic, approx 80% of adults in the united states are seropositive, but in no case has the virus been implicated as the etiological agent for a human disease. aav is a defective parvovirus with a single-stra ... | 2001 | 21394584 |
| metabolic activities and chondrogenic differentiation of human mesenchymal stem cells following recombinant adeno-associated virus-mediated gene transfer and overexpression of fibroblast growth factor 2. | the genetic manipulation of bone marrow-derived mesenchymal stem cells (mscs) is an attractive approach to produce therapeutic platforms for settings that aim at restoring articular cartilage defects. here, we examined the effects of recombinant adeno-associated virus (raav)-mediated overexpression of human fibroblast growth factor 2 (hfgf-2), a mitogenic factor also known to influence msc differentiation, upon the proliferative and chondrogenic activities of human mscs (hmscs) in a three-dimens ... | 2011 | 21417714 |
| adeno-associated virus serotype 2 mediated transduction and coexpression of the human apoai and sr-bi gene in hepg2 cells. | cholesterol efflux is the first step in the reverse cholesterol transport (rct) pathway, removing excess cholesterol from tissues, including the arterial wall, thus preventing the development of atherosclerosis. adeno-associated virus (raav) has demonstrated significant promise as a dna-delivery vector to treat serious human diseases. in this study, we constructed recombinant adeno-associated viruses coexpressing apoai and sr-bi successfully, the double gene mrna and protein were both strongly e ... | 2011 | 21431865 |
| preclinical evaluation of gene delivery methods for the treatment of loco-regional disease in breast cancer. | preclinical results with various gene therapy strategies indicate significant potential for new cancer treatments. however, many therapeutics fail at clinical trial, often due to differences in tissue physiology between animal models and humans, and tumor phenotype variation. clinical data relevant to treatment strategies may be generated prior to clinical trial through experimentation using intact patient tissue ex vivo. we developed a novel tumor slice model culture system that is universally ... | 2011 | 21444371 |
| intravenous gene therapy with pim-1 via a cardiotropic viral vector halts the progression of diabetic cardiomyopathy through promotion of prosurvival signaling. | rationale: studies in transgenic mice showed the key role of (pim-1) (proviral integration site for moloney murine leukemia virus-1) in the control of cardiomyocyte function and viability. objective: we investigated whether pim-1 represents a novel mechanistic target for the cure of diabetic cardiomyopathy, a steadily increasing cause of nonischemic heart failure. methods and results: in streptozotocin-induced type 1 diabetic mice, pim-1 protein levels declined during progression of cardiomyopat ... | 2011 | 21474815 |
| preclinical differences of intravascular aav9 delivery to neurons and glia: a comparative study of adult mice and nonhuman primates. | other labs have previously reported the ability of adeno-associated virus serotype 9 (aav9) to cross the blood-brain barrier (bbb). in this report, we carefully characterized variables that might affect aav9's efficiency for central nervous system (cns) transduction in adult mice, including dose, vehicle composition, mannitol coadministration, and use of single-stranded versus self-complementary aav. we report that aav9 is able to transduce approximately twice as many neurons as astrocytes acros ... | 2011 | 21487395 |
| aav mediated gdnf secretion from retinal glia slows down retinal degeneration in a rat model of retinitis pigmentosa. | mutations in over 80 identified genes can induce apoptosis in photoreceptors, resulting in blindness with a prevalence of 1 in 3,000 individuals. this broad genetic heterogeneity of disease impacting a wide range of photoreceptor functions renders the design of gene-specific therapies for photoreceptor degeneration impractical and necessitates the development of mutation-independent treatments to slow photoreceptor cell death. one promising strategy for photoreceptor neuroprotection is neurotrop ... | 2011 | 21522134 |
| a non membrane-targeted human soluble cd59 attenuates choroidal neovascularization in a model of age related macular degeneration. | age related macular degeneration (amd) is the most common cause of blindness amongst the elderly. approximately 10% of amd patients suffer from an advanced form of amd characterized by choroidal neovascularization (cnv). recent evidence implicates a significant role for complement in the pathogenesis of amd. activation of complement terminates in the incorporation of the membrane attack complex (mac) in biological membranes and subsequent cell lysis. elevated levels of mac have been documented o ... | 2011 | 21552568 |
| adeno-associated virus-mediated human acidic fibroblast growth factor expression promotes functional recovery of spinal cord-contused rats. | background: following spinal cord injury, delivery of neurotrophic factors to the injured spinal cord has been shown to promote axonal regeneration and functional recovery. in previous studies, we showed that acidic fibroblast growth factor (afgf) is a potent neurotrophic factor that promotes the regeneration of axotomized spinal cord or dorsal root ganglion neurons. methods: we constructed a recombinant adeno-associated virus (aav) vector to express human afgf and evaluated afgf expression and ... | 2011 | 21557400 |
| capsid-specific t-cell responses to natural infections with adeno-associated viruses in humans differ from those of nonhuman primates. | hepatic adeno-associated virus serotype 2 (aav2)-mediated gene transfer failed to achieve sustained transgene product expression in human subjects. we formulated the hypothesis that rejection of aav-transduced hepatocytes is caused by aav capsid-specific cd8(+) t cells that become reactivated upon gene transfer. although this hypothesis was compatible with clinical data, which showed a rise in circulating aav capsid-specific t cells following injection of aav vectors, it did not explain that aav ... | 2011 | 21587208 |
| effect of soluble icam-1 on a sjögren's syndrome-like phenotype in nod mice is disease stage dependent. | intercellular adhesion molecule-1 (icam-1) is involved in migration and co-stimulation of t and b cells. membrane bound icam-1 is over expressed in the salivary glands (sg) of sjögren's syndrome (ss) patients and has therefore been proposed as a potential therapeutic target. to test the utility of icam-1 as a therapeutic target, we used local gene therapy in non obese diabetic (nod) mice to express soluble (s)icam-1 to compete with membrane bound icam-1 for binding with its receptor. therapy was ... | 2011 | 21589878 |
| vector characterization methods for quality control testing of recombinant adeno-associated viruses. | adeno-associated virus (aav)-based vectors expressing therapeutic gene products have shown great promise for human gene therapy. a major challenge for translation of promising research to clinical development is the establishment of appropriate quality control (qc) test methods to characterize clinical grade aav vectors. this chapter focuses on qc testing, providing an overview of characterization methods appropriate for clinical vectors prepared for early phase clinical studies, and detailed de ... | 2011 | 21590401 |
| direct comparison of four adeno-associated virus serotypes in mediating the production of antiangiogenic proteins in mouse muscle. | to determine the adeno-associated virus (aav) serotype that most efficiently mediates muscle expression of antiangiogenic proteins, we injected four different serotype (1, 2, 7, and 8) aav vectors encoding mouse endostatin (mend) or human soluble flk-1 (hsflk-1) into a quadriceps muscle of c57bl/6 mice. the highest plasma levels of therapeutic protein were observed in aav8-injected mice (8 > 7 > 1 > 2). sustained expression of mend was detected for 6 months, whereas concentrations of hsflk-1 dec ... | 2011 | 21599511 |
| aav2-mediated subretinal gene transfer of hifn-α attenuates experimental autoimmune uveoretinitis in mice. | recent reports show that gene therapy may provide a long-term, safe and effective intervention for human diseases. in this study, we investigated the effectiveness of adeno-associated virus 2 (aav2) based human interferon-alpha (hifn-α) gene therapy in experimental autoimmune uveoretinitis (eau), a classic model for human uveitis. | 2011 | 21611186 |
| an universal real-time pcr for the detection and quantification of adeno-associated virus serotype 2 derived inverted terminal repeat sequences. | viral vectors based on different naturally occurring adeno-associated virus (aav) serotypes belong to the most promising tools in human gene therapy. for the production of recombinant aav (raav) vectors, researchers are focusing predominantly on cross-packaging an artificial aav genome based on serotype 2 (aav2) into the capsids derived from other serotypes. within the packaged genome the inverted terminal repeats (itrs) are the only cis-acting viral elements required for raav vector generation ... | 2011 | 21644816 |
| duchenne muscular dystrophy gene therapy: lost in translation? | a milestone of molecular medicine is the identification of dystrophin gene mutation as the cause of duchenne muscular dystrophy (dmd). over the last 2 decades, major advances in dystrophin biology and gene delivery technology have created an opportunity to treat dmd with gene therapy. remarkable success has been achieved in treating dystrophic mice. several gene therapy strategies, including plasmid transfer, exon skipping, and adeno-associated virus-mediated microdystrophin therapy, have entere ... | 2011 | 21691429 |
| 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 |
| dosage thresholds for aav2 and aav8 photoreceptor gene therapy in monkey. | gene therapy is emerging as a therapeutic modality for treating disorders of the retina. photoreceptor cells are the primary cell type affected in many inherited diseases of retinal degeneration. successfully treating these diseases with gene therapy requires the identification of efficient and safe targeting vectors that can transduce photoreceptor cells. one serotype of adeno-associated virus, aav2, has been used successfully in clinical trials to treat a form of congenital blindness that requ ... | 2011 | 21697530 |
| hepatorenal correction in murine glycogen storage disease type i with a double-stranded adeno-associated virus vector. | glycogen storage disease type ia (gsd-ia) is caused by the deficiency of glucose-6-phosphatase (g6pase). long-term complications of gsd-ia include life-threatening hypoglycemia and proteinuria progressing to renal failure. a double-stranded (ds) adeno-associated virus serotype 2 (aav2) vector encoding human g6pase was pseudotyped with four serotypes, aav2, aav7, aav8, and aav9, and we evaluated efficacy in 12-day-old g6pase (-/-) mice. hypoglycemia during fasting (plasma glucose <100-ámg/dl) was ... | 2011 | 21730973 |
| electrospun nanofibrous scaffolds for controlled release of adeno-associated viral vectors. | the integration of viral gene delivery with key features of biomaterial scaffolds that modulate viral delivery in a controlled manner offers a promising strategy for numerous tissue engineering applications. in this study adeno-associated virus (aav), which is widely utilized in human gene therapy as a gene carrier due to its safety and efficient gene delivery capability, was encapsulated within electrospun nanofibrous scaffolds composed of blended mixtures of elastin-like polypeptides (elp) and ... | 2011 | 21745607 |
| 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 |
| site-specific integration by the adeno-associated virus rep protein. | inserting genetic information at precise locations into the human genome has been the goal of gene transfer technology for almost two decades. the spectacular progress of mammalian genetics in the last two decades has led to the development of technology for genome editing and homologous recombination in human somatic cells that is finally approaching efficiency compatible with clinical application. site-specific integration, or the insertion of genes at known locations by enzymes with target re ... | 2011 | 21827397 |
| magnetically enhanced adeno-associated viral vector delivery for human neural stem cell infection. | gene therapy technology is a powerful tool to elucidate the molecular cues that precisely regulate stem cell fates, but developing safe vehicles or mechanisms that are capable of delivering genes to stem cells with high efficiency remains a challenge. in this study, we developed a magnetically guided adeno-associated virus (aav) delivery system for gene delivery to human neural stem cells (hnscs). magnetically guided aav delivery resulted in rapid accumulation of vectors on target cells followed ... | 2011 | 21840595 |
| computationally designed adeno-associated virus (aav) rep 78 is efficiently maintained within an adenovirus vector. | adeno-associated virus (aav) is a single-stranded parvovirus retaining the unique capacity for site-specific integration into a transcriptionally silent region of the human genome, a characteristic requiring the functional properties of the rep 78/68 polypeptide in conjunction with aav terminal repeat integrating elements. previous strategies designed to assemble these genetic elements into adenoviral (ad) backbones have been limited by the general intolerability of aav rep sequences, prompting ... | 2011 | 21844368 |
| Differential virus restriction patterns of rhesus macaque and human APOBEC3A: implications for lentivirus evolution. | The human apolipoprotein B mRNA editing enzyme catalytic peptide-like 3 (APOBEC3; A3) family of proteins (A3A-H) are known to restrict various retroviruses and retroelements, but the full complement of rhesus macaque A3 proteins remains unclear. We report the isolation and characterization of the hA3A homologue from rhesus macaques (rhA3A) and show that the rhesus macaque and human A3 genes are orthologous. RhA3A is expressed at high levels in activated CD4+ T cells, is widely expressed in macaq ... | 2011 | 21868050 |
| development of the hybrid sleeping beauty-baculovirus vector for sustained gene expression and cancer therapy. | antiangiogenesis is an appealing anticancer approach but requires continued presence of the antiangiogenic agents, which can be remedied by gene therapy. baculovirus is an emerging gene delivery vector but only mediates transient expression (<7 days); thus, this study primarily aimed to develop a hybrid baculovirus for sustained antiangiogenic gene expression and cancer therapy. we first constructed plasmids featuring adeno-associated virus inverted terminal repeats (aav itrs), orip/epstein-barr ... | 2011 | 21918552 |
| advancements in adeno-associated viral gene therapy approaches: exploring a new horizon. | gene therapy is a promising new therapeutic strategy that has been explored in a wide variety of diseases, ranging from cancer to hemophilia, and ocular disorders to autoimmune diseases, among others. proof of concept of gene transfer approaches has been shown in over 100 studies of animal models of disease, although only a few are under development for clinical application. the us food and drug administration and the european medicines agency have not approved any viral human gene therapy produ ... | 2011 | 21941595 |
| novel random peptide libraries displayed on aav serotype 9 for selection of endothelial cell-directed gene transfer vectors. | we have demonstrated the potential of random peptide libraries displayed on adeno-associated virus (aav)2 to select for aav2 vectors with improved efficiency for cell type-directed gene transfer. aav9, however, may have advantages over aav2 because of a lower prevalence of neutralizing antibodies in humans and more efficient gene transfer in vivo. here we provide evidence that random peptide libraries can be displayed on aav9 and can be utilized to select for aav9 capsids redirected to the cell ... | 2011 | 21956692 |
| Production of recombinant adeno-associated viral vectors and use in in vitro and in vivo administration. | Adeno-associated virus is a nonpathogenic human virus that has been developed into a gene-delivery vector due to its high efficiency of infection for many different cell types and its ability to persist and lead to long-term gene expression. 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, along with methods to quantify the viral vectors. Two detailed metho ... | 2011 | 21971848 |
| virus infection recognition and early innate responses to non-enveloped viral vectors. | numerous human genetic and acquired diseases could be corrected or ameliorated if viruses are harnessed to safely and effectively deliver therapeutic genes to diseased cells and tissues in vivo. innate immune and inflammatory response represents one of the key stumbling blocks during the development of viral-based therapies. in this review, current data on the early innate immune responses to viruses and to the most commonly used gene therapy vectors (using adenovirus and adeno-associated virus) ... | 2010 | 21994609 |
| Injection of AAV2-BMP2 and AAV2-TIMP1 into the nucleus pulposus slows the course of intervertebral disc degeneration in an in vivo rabbit model. | BACKGROUND CONTEXT: Intervertebral disc degeneration (IDD) is a common cause of back pain. Patients who fail conservative management may face the morbidity of surgery. Alternative treatment modalities could have a significant impact on disease progression and patients' quality of life. PURPOSE: To determine if the injection of a virus vector carrying a therapeutic gene directly into the nucleus pulposus improves the course of IDD. STUDY DESIGN: Prospective randomized controlled animal study. MET ... | 2011 | 22023960 |
| normal collagen and bone production by gene-targeted human osteogenesis imperfecta ipscs. | osteogenesis imperfecta (oi) is caused by dominant mutations in the type i collagen genes. in principle, the skeletal abnormalities of oi could be treated by transplantation of patient-specific, bone-forming cells that no longer express the mutant gene. here, we develop this approach by isolating mesenchymal cells from oi patients, inactivating their mutant collagen genes by adeno-associated virus (aav)-mediated gene targeting, and deriving induced pluripotent stem cells (ipscs) that were expand ... | 2011 | 22031238 |
| AAV-Mediated Gene Transfer of Human X-Linked Inhibitor of Apoptosis Protects against Oxidative Cell Death in Human RPE Cells. | Purpose. To determine whether human X-linked inhibitor of apoptosis (XIAP) enhances the survival of cultured human retinal pigment epithelial cells exposed to H(2)O(2). Methods. ARPE-19 cells were exposed to H(2)O(2) to induce oxidative cell death. Intracellular reactive oxygen species (ROS) were measured using 2',7'-dichlorofluorescein diacetate. MTT assay was performed to quantify mitochondrial stress. Cell apoptosis was determined by TUNEL assay. Human XIAP was delivered with bicistronic exp ... | 2011 | 22039248 |
| Epirubicin potentiates rAAV2/5-mediated TRAIL expression in fibroblast-like synoviocytes and augments the anti-arthritis effects of rAAV2/5-TRAIL. | OBJECTIVE.: Synovial cells in rheumatoid synovium display abnormal proliferation, which leads to joint destruction. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been described as a pro-apoptotic factor in fibroblast-like synoviocytes (FLSs). This study was undertaken to investigate the functions of recombinant adeno-associated virus (rAAV2/5)-TRAIL in FLSs and arthritic mice. METHODS.: Primary human FLSs were infected with rAAV2/5-TRAIL in the presence or absence of ... | 2011 | 22131069 |
| concerted nicking of donor and chromosomal acceptor dna promotes homology-directed gene targeting in human cells. | the exchange of genetic information between donor and acceptor dna molecules by homologous recombination (hr) depends on the cleavage of phosphodiester bonds. although double-stranded and single-stranded dna breaks (ssbs) have both been invoked as triggers of hr, until very recently the focus has been primarily on the former type of dna lesions mainly due to the paucity of ssb-based recombination models. here, to investigate the role of nicked dna molecules as hr-initiating substrates in human s ... | 2011 | 22189101 |