Paul robbins methods in molecular medicine 1997 humana press. Takeda 2002 adenoassociated virus vectormediated gene transfer into dystrophindeficient skeletal muscles encounters elevated immune response against the transgene product, gene therapy, 9. Adenovirusmediated e2epf ucp gene transfer prevents. Innate immune response after adenoviral gene delivery into. Gomez foix, am, ws coats, s baque, t alam, rd gerard, cb newgard 1992 adenovirusmediated transfer of the muscle glycogen phosphorylase gene into hepatocytes confers altered regulation of glycogen metabolism. Adenovirusassociated virus vectormediated gene transfer. The results suggest that adenovirusmediated il12 gene transfer combined with ad. Gene transfer mediated by viral vectors is referred to as transduction. The efficiency of adenovirusmediated gene transfer is now well established. Adenovirusmediated efficient gene transfer into cultured. Cbcftr contains the cytomegalovirus cmv enhancer, jactin promoter, hu man cftr cdna, and sv40 polya minigene cassette in serted into the eldeleted region spanning 1. Increasing doses of adenoviral vector expressing tgf. Anionic liposomes increase the efficiency of adenovirus.
Adenovirusmediated gene transfer using insitu perfusion of. Results characteristics of the study participants six men with severe hemophilia b fix activity, primates. Adenovirus mediated gene transfer into the 3d organoids provides an efficient approach to genetic manipulations of stem cellbased selforganizing tissuelike structures the use of adenovirus vectors in 3d organoid culture offers several unparalleled advantages, compared with other gene delivery approaches including retroviral or lentiviral. Use of adenovirus vectors for therapeutic gene delivery shows broad potential. In vitro and in vivo asessment of adenovirus 41 as a vector for gene. Recombinant adenovirus vectors containing expression cassettes for human cystic fibrosis transmembrane conductance regulator cftr and escherichia coli betagalactosidase lacz were instilled. The transplantation of primary mammary epithelial cells after adenoviruscremediated recombination provides a new approach for the study of specific gene function during mammary gland development and in breast cancer. Generally, once bound to its receptor, a virus enters the cell via clathrinmediated. To obtain the sustained serum antibody concentration with one single injection and lower the cost of antibody protein therapy, an adenovirusmediated fulllength antibody gene therapy was developed. Adenovirusmediated gene transfer into the 3d organoids provides an efficient approach to genetic manipulations of stem cellbased selforganizing tissuelike structures the use of adenovirus vectors in 3d organoid culture offers several unparalleled advantages, compared with other gene delivery approaches including retroviral or lentiviral. Influence of temperature on adenovirusmediated gene transfer.
Therefore, we studied how those factors affect adenovirus mediated gene transfer to the ischemic brain. Inthiscontext,allanalyseswerecarriedout24h after ad. Rsv,bgalinfected cells couldproliferate anddifferentiate andthedaughtercells expressthelaczgene. Adverse effects of adenovirusmediated gene transfer of human. Pdf although adenovirus can infect a wide range of cell types, lymphocytes are not generally susceptible to adenovirus infection, in part because of. To establish an efficient technique for adenovirusmediated gene transfer in liver transplantation, we evaluated the in situ perfusion of liver grafts. Pdf influence of temperature on adenovirusmediated gene. A technical challenge is the scalability of increasingly complex nanoparticle designs for large animal and human use. Identification of coagulation factor fx binding sites on the adenovirus serotype 5 hexon. Despite remarkable progress in the research of both viral and nonviral gene delivery vectors, the drawbacks in each delivery system have limited their clinical applications. The purpose of this study was to compare levels and patterns of expression of reporter genes achieved with an e1deleted and partially e3deleted.
Intraocular adenoviral vectormediated gene transfer in. In gene therapy a gene that is intended for delivery is packaged into a replicationdeficient viral particle to form a viral vector. As noted above, the efficacy of adenovirus mediated gene transfer after i. Methods for delivery of genes to hepatocytes in vivo using recombinant adenovirus vectors. Adenoassociated virus aav, an ssdna member of the family parvoviridae, was discovered fortuitously by researchers working with adenovirus. Plasmids containing recombinant canine adenovirus cav vectors from which the e1. Gene transfer mediated by nonviral vectors is referred to as transfection. The purpose of this study was to compare levels and patterns of expression of reporter genes achieved with an e1deleted and partially e3 deleted. In this chapter, the advantages of adenoviral vector mediated gene transfer for cardiovascular disease applications, and the methods on how to construct, propagate, and evaluate adenoviral vectors, are discussed.
Delayed cerebral vasospasm after subarachnoid hemorrhage sah may be caused by multiple and complex mechanisms, including vascular dysfunction caused by oxidative stress. Adverse effects of adenovirusmediated gene transfer of human transforming growth factor beta 1 into rabbit knees zhibao mi, 1 steven c ghivizzani, 1, 3 eric lechman, 1 joseph c glorioso, 1 christopher h evans, 2, 3 and paul d robbins 1. Pdf adenoviralmediated gene transfer in lymphocytes. Engelhardt, yiping yang, monica zepeda, sara weberpendleton, mariann grossman, and james m. Adenoviruses are used extensively as gene transfer agents, both experimentally and clinically.
High efficiency adenovirusmediated gene transfer to human. We tested adlacz transgene expression at the dosage of 10 9, 10 10, or 10 11 particles per injection to determine the suitable experimental dosage of adfasl in the in vivo rascid model. Targeting of adenovirusmediated gene transfer the capacity to target a foreign gene to the intended cell type and to express that gene in a tissuespecific and regulatable manner are potentially critical to the successful application of genebased ther apeutic strategies, since promiscuous and constitutive expression of foreign genes may have. Adenovirusmediated transfer of the cftr gene to lung of nonhuman primates. Adenovirus associated virus vector mediated gene transfer in hemophilia b article pdf available in new england journal of medicine 36525. May 24, 2005 the results suggest that adenovirus mediated il12 gene transfer combined with ad. Gene therapy may be a promising approach for treatment of brain ischemia. Using an adenoviral vector with high titre, adenovirusmediated hsvtk gene therapy administered locally, intraoperatively, and in conjunction with subsequent intravenous ganciclovir has been developed for the treatment of operable highgrade glioma. Adenoviruses and other viruses are highly efficient at transferring their dna into a target cell. Here, we investigated the effect of ucp gene transfer on therapeutic angiogenesis. Applications of adenoviral vectormediated gene transfer in.
We have previously shown that prolonged retention of rad vectors in the circulation by liver bypass improves the transduction of renal glomerular cells in adult mice and rats. In the present studies we describe tumor growth inhibition. Adenovirus vector mediated dose dependent transgene expression in human synovial tissues in vivoin scid mice. To evaluate this concept, a hollow, helicaltipped penetrating catheter was used to deliver vectorcontaining fluid directly into the intrapericardial space. Influence of temperature on adenovirusmediated gene.
Adenovirus mediated p53 gene transfer in advanced nonsmallcell lung cancer stephen g. Targeted expression of desired therapeutic proteins within the tumor is the best approach to reduce toxicity and improve survival. Human adenovirus types 2 and 5 were chosen as potential gene transfer vectors. Gene transfer of extracellular superoxide dismutase. In the current study, adenoviral vectors were formulated with anionic liposomes to protect.
In comparison to transfection efficiency of the homologous expression plasmid, adenovirus mediated gene transfer was substantially more efficient. Pdf adenovirusassociated virus vectormediated gene. An icosahedral, nonenvel oped virus with broad tropism, adenovirus can infect both dividing and quiescent cells. Adenoviral vectormediated insulin gene transfer in the mouse pancreas corrects streptozotocininduced hyperglycemia. Cpdphotolyase adenovirusmediated gene transfer in normal and dnarepairdeficient human cells vanessa chigancas, alain sarasin, carlos frederico martins menck journal of cell science 2004 117. In cell culture, the adenovirus serotype 5 fiber protein engages the coxsackievirus and adenovirus receptor car to bind cells. In preparation for human trials of gene therapy for cystic fibrosis cf, we performed a preclinical study of gene transfer into the lungs of baboons. Paradoxically, following intravascular delivery, car is not used for liver. The achilles heel of adenoviral gene therapy is its immunogenicity and many aspects of adenovirus induced cutaneous immune reaction still remain unanswered, particularly the role of. In this study, we generated a new technology for spatiotemporally controllable gene therapy. Efficient, repeated adenovirusmediated gene transfer in mice. Herz, j and rd gerard 1993 adenovirusmediated transfer of low density.
The 293aav cell line is a permanent line established from primary embryonic human kidney. Adenovirusassociated virus vector mediated gene transfer in. Gene therapy using adenovirusmediated fulllength anti. Therapeutic monoclonal antibody is increasingly applied in many clinical applications, although complicated technologies and high cost still limit their wide applications. Recombinant adenovirus carrying p27kip1 gene can obviously inhibit the growth of transplantable model of human esophageal carcinoma in nude mice. Adenovirusmediated gene transfer to ischemic brain. Adenoviral vectormediated insulin gene transfer alexander. Adenovirusmediated gene transfer article in methods in molecular biology clifton, n. Mar 12, 2003 to examine the effect of transforming growth factor tgf. Dec 22, 2011 at present, gene transfer mediated by an adenovirusassociated virus aav vector shows the greatest promise for longterm correction of hemophilia b in the preclinical setting. This process is mediated through endocytosis after adenovirus. In patients with cystic fibrosis, adenoviralvectormediated transfer of the cftr gene did not correct functional defects in nasal epithelium, and local inflammatory responses limited the dose. Adenoviral vector with shield and adapter increases tumor. Jul 12, 20 to add to the armamentarium of local therapies, gene therapy was reassessed with an improved agent.
Use of recombinant adenovirus for metabolic engineering of. Gene therapy is expected to be utilized for the treatment of various diseases. Adenovirus serotype 5 hexon mediates liver gene transfer. Gene therapy with tumorspecific promoter mediated suicide. Adenovirusmediated gene transfer to glomerular cells in. Positive selection of thymocytes induced by gene transfer. However, there are drawbacks to using viruses to deliver genes into cells. A controlled study of adenoviralvectormediated gene.
Expression of transgene is affected by several factors, including host conditions and intervals after gene transfer. Viruses used for gene therapy to date include retrovirus, adenovirus, adenoassociated virus and herpes simplex virus. Nettelbeck1 1 oncolytic adenovirus group, german cancer research center dkfz, heidelberg, germany 2 molecular oncosurgery, german cancer research center. Adenovirusmediated gene transfer via intraperitoneal injection is known to induce gene expression in the intraperitoneal tissues, including liver, pancreas, spleen, and mesenterium. Engineered adenoviruses combine enhanced oncolysis with. Since the original idea of vectorbased gene therapy, a great deal of progress in. Combined gene therapy strategy with recombinant adenovirus expressing horseradish peroxidase hrp mediated by human. The implanted human synovium only or with cartilage was harvested three days after virus. Influence of temperature on adenovirus mediated gene transfer. However, targeting of liver cells by adenoviruses compromises their potential efficacy. E2epf ubiquitin carrier protein ucp stabilizes hypoxiainducible factor1. At present, gene transfer mediated by an adenovirusassociated virus aav vector shows the greatest promise for longterm correction of hemophilia b in the preclinical setting. We hypothesized that efficient adenovirus mediated gene expression in pericardial lining mesothelium could be achieved by transmyocardial vector delivery to the pericardium. Cd followed by 5fc treatment may be useful for treating cancers.
However, the spatiotemporal resolution of current gene therapy technology is not high enough. Sooyeon kim, sangjin lee, hyokyung han, soojeong lim. Protective effects of fcfused pdl1 on two different. Adenoviral mediated gene transfer how is adenoviral. Methods for human skin gene therapy requires efficient and stable introduction of genes into skin cells. Adenovirusmediatedefficientgenetransferintoculturedthreedimensionalorganoids pone. Using an adenoviral vector with high titre, adenovirus mediated hsvtk gene therapy administered locally, intraoperatively, and in conjunction with subsequent intravenous ganciclovir has been developed for the treatment of operable highgrade glioma. Apr 11, 2011 gene therapy is a promising therapeutic approach for cancer.
Adenovirusassociated virus vector mediated gene transfer. Methods preparation of recombinant adenovirus the recombinant cftr adenovirus ad. At present, gene transfer mediated by an adenovirus associated virus aav vector shows the greatest promise for longterm correction of hemophilia b in the preclinical setting. Generally, once bound to its receptor, a virus enters the cell via clathrin mediated. Adenovirusmediated gene therapy with sitimagene ceradenovec.
Pdf phase i study of a recombinant adenovirusmediated. The adenoviruses used for gene therapy, however, are rendered replication defective by removal of the early 1 e1 region that is vital for transformation and viral. Nonviral vectors are considered to be much safer than viral vectors, but at present, they are fairly inefficient at transferring genes. Most mammaryglandspecific promoters identified to date are regulated by lactogenic hormones. They are expressed predominantly in lobuloalveolar cells during. Examples of the utility of recombinant adenovirus for studies on metabolic. We found that adenovirusmediated gene transfer in mesenchymal stem cells can be significantly enhanced by the cationic polymer polybrene. Phase i study of a recombinant adenovirusmediated gene transfer in lung cancer patients. Efficient in vivo catheterbased pericardial gene transfer. We hypothesized that efficient adenovirusmediated gene expression in pericardial lining mesothelium could be achieved by transmyocardial vector delivery to the pericardium. Adverse effects of adenovirus mediated gene transfer of human transforming growth factor beta 1 into rabbit knees zhibao mi, 1 steven c ghivizzani, 1, 3 eric lechman, 1 joseph c glorioso, 1 christopher h evans, 2, 3 and paul d robbins 1. Seroswitch adenovirusmediated in vivo gene transfer. Adenovirusmediated p53 gene transfer in advanced nonsmall.
To add to the armamentarium of local therapies, gene therapy was reassessed with an improved agent. This study is to establish a more effective and less toxic gene therapy of cancer. Cytokine gene transfer using multiple intratumoral injections can induce tumor regression in several animal models, but this administration technique limits the use for human gene therapy. Aminoclay as a highly effective cationic vehicle for enhancing adenovirusmediated gene transfer through nanobiohybrid complex formation. Adenovirusmediated interleukin12 gene transfer combined. Recombinant aav2 is the most common serotype used in gene delivery, and can be produced at high titers with a helper virus or cell biolabs aav helperfree system in 293 cells. This page was last edited on 9 october 2019, at 21. Adenovirus interactions with host factors and gene therapy. We introduced optogenetic and crisprcas9 techniques into a recombinant adenovirus ad vector, which is widely used in clinical.
Targeting of adenovirus mediated gene transfer the capacity to target a foreign gene to the intended cell type and to express that gene in a tissuespecific and regulatable manner are potentially critical to the successful application of gene based ther apeutic strategies, since promiscuous and constitutive expression of foreign genes may have. The systemic delivery of recombinant adenoviral rad vectors to renal glomeruli has been problematic due to the rapid clearance of the circulating virus by the liver. Gene transfer using adenoviral vectors has shown promising results in animal studies, and is now being tested in many clinical trials. Circumventing the immune response to adenovirusmediated gene therapy. Transient cutaneous gene therapy is an attractive approach in the treatment of skin diseases. Cpdphotolyase adenovirusmediated gene transfer in normal. Adenovirusmediated gene transfer to treat neurologic disease. Results characteristics of the study participants six men with severe hemophilia b fix activity, adenovirus mediated genetransfer, the studywasdesignedtoanalyze direct lacztransfer andexpression before the timethe ad. Elimination of rheumatoid synovium in situ using a fas. Adenovirusmediated gene transfer to retinal ganglion cells. Adverse effects of adenovirusmediated gene transfer of.
Adenovirusencoded ucp adfucp increased the expression of vascular endothelial growth factor vegf and fibroblast growth factor2 fgf2 in cells and mice. There has been a longlasting interest in using viral vectors, especially adenoviral vectors, to deliver therapeutic genes for the past two decades. Engineered adenoviruses combine enhanced oncolysis with improved virus production by mesenchymal stromal carrier cells katharina hammer1, adam kazcorowski2, li liu 2, michael behr1, peter schemmer3, ingrid herr and dirk m. Mastrangeli a, harvey b g, yao j, wolff g, kovesdi i, crystal r g, falckpedersen e. Generation of optogenetically modified adenovirus vector for. To examine the effect of transforming growth factor tgf. Therefore, one of the concepts for developing novel vectors is to overcome the limitations of individual vectors by combining them. Wilson abstract in preparation for hunian trials of gene therapy for cystic fibrosis cf, we performed a preclinical study of.
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