Abstract:
:Recombinant adeno-associated virus (rAAV)-mediated gene transfer has shown promise for treating diseases in various animal models including the mdx mouse model of Duchenne muscular dystrophy (DMD). In many cases, however, preclinical studies in inbred mice have not successfully predicted human clinical responses. To assess the potential clinical utility of treating human DMD patients by AAV-mediated gene delivery, we performed a series of direct intramuscular injections in random-bred wild-type dogs. AAV serotypes 2 and 6 carrying different promoter-transgene cassettes were produced as previously described for murine studies and administered intramuscularly. The injection sites were biopsied at various time points and analyzed for transgene expression and immunohistochemical analysis. In contrast to the generally nonimmunogenic nature of these vectors in murine studies, both AAV2 and AAV6 vectors elicited robust cellular immune responses regardless of the transgene expressed, the cellular specificity of the promoter, and the muscle type injected. Viral purification by various methods did not diminish T cell-mediated infiltration. Our data indicate that AAV2 and AAV6 capsid proteins can elicit primary cellular immune responses when injected into the skeletal muscle of random-bred dogs, and suggest the possibility of cellular immunity to AAV vectors in humans.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Wang Z,Allen JM,Riddell SR,Gregorevic P,Storb R,Tapscott SJ,Chamberlain JS,Kuhr CSdoi
10.1089/hum.2006.093subject
Has Abstractpub_date
2007-01-01 00:00:00pages
18-26issue
1eissn
1043-0342issn
1557-7422journal_volume
18pub_type
杂志文章abstract::The objective of this phase II investigation is to assess the safety and efficacy of a plasmid mediated approach to induce angiogenesis/arteriogenesis with the angiomatrix protein Del-1 (developmentally regulated endothelial locus 1), in subjects with intermittent claudication (IC) secondary to peripheral arterial dis...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1089/104303404323142060
更新日期:2004-06-01 00:00:00
abstract::Engineering gene therapy vectors to modulate the immune response is an important goal. In this regard, costimulation of T cells is a critical determinant in immune activation. The costimulatory molecule CD40, expressed on antigen-presenting cells, is thought to interact with CD40 ligand (CD40L) expressed on activated ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401750214302
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abstract::Baculovirus vectors recently have been shown to be capable of efficient transduction of human hepatoma cells and primary hepatocytes in culture. This paper describes the generation of a novel recombinant baculovirus (VGZ3) in which the vesicular stomatitis virus glycoprotein G (VSV G) is present in the viral envelope....
journal_title:Human gene therapy
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doi:10.1089/hum.1997.8.17-2011
更新日期:1997-11-20 00:00:00
abstract::Immunoisolation of allogeneic cells within a membrane-bound device is a unique approach for gene therapy. We employed an immunoisolation device that protects allograft, but not xenograft, cells from destruction, to implant a human fibroblast line (MSU 1.2) in athymic rodents. Cells, transduced with the MFG-human facto...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.6-879
更新日期:1998-04-10 00:00:00
abstract::Hematopoietic stem cells (HSCs) are a potential target for the retrovirus-mediated transfer of chemotherapeutic drug resistance genes. For integration of the proviral DNA in the HSC genome cell division is required. In the bone marrow (BM) hematopoiesis occurs in the vicinity of stroma cells. Soluble stroma components...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950017789
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abstract::Esophageal cancer is characterized by rapid clinical progression and poor prognosis, due to early-stage invasion of adjacent tissues and metastasis. Tissue factor pathway inhibitor-2 (TFPI-2) has been implicated as a metastasis-associated gene in many types of tumors. Here we describe the potential involvement of TFPI...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2008.129
更新日期:2009-01-01 00:00:00
abstract::The potential of short interfering RNA (siRNA) to be developed for therapeutic use against cancer depends on the availability of an efficient tumor-specific delivery vehicle. We have previously shown that a nanoscale nonviral liposome-based complex that includes an anti-transferrin receptor single-chain antibody fragm...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.117
更新日期:2006-01-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401753153938
更新日期:2001-10-10 00:00:00
abstract::Glycogen storage disease type II (GSD-II) is a lethal, autosomal recessive metabolic myopathy caused by a lack of acid-alpha-glucosidase (GAA) activity in the cardiac and skeletal muscles. Absence of adequate intralysosomal GAA activity results in massive amounts of glycogen accumulation in multiple muscle groups, res...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401750195917
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.15-1883
更新日期:1996-10-01 00:00:00
abstract::The clinical success of suicide gene therapy using herpes simplex virus type 1 thymidine kinase (TK) is largely dependent on the capacity of this enzyme to effectively induce the death of bystander cells. We have shown that fusion of TK to an 11-amino acid peptide from the basic domain of the human immunodeficiency vi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2005.16.1389
更新日期:2005-12-01 00:00:00
abstract::Gene-modified replication-competent adenoviruses (Ads) are emerging as a promising new modality for the treatment of cancer. We have previously shown that E1B 19kDa and E1B 55kDa gene-deleted Ad (Ad-DeltaE1B19/55) exhibits improved tumor-specific replication and cell lysis, leading to an enhanced antitumor effect. In ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.167
更新日期:2007-09-01 00:00:00
abstract::Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrogenesis. Transforming growth factor beta 1 (TGF-β1) and platelet-derived growth factor (PDGF) are key profibrotic cytokines that regulate HSC activation and proliferation with functional convergence. Dual RNA interference against their ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.047
更新日期:2019-02-01 00:00:00
abstract::Newcastle disease virus (NDV) is a naturally oncolytic virus that has been shown to be safe and effective for cancer therapy. Tumor virotherapy using NDV emerged in the 1950s and has advanced more recently by the increased availability of reverse genetics technology. In this study, we constructed a reverse genetics sy...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.207
更新日期:2012-07-01 00:00:00
abstract::Glioblastomas account for approximately 20% of all primary brain tumors in adults. Glioblastoma multiforme (GBM) is a highly malignant tumor. In spite of advances in surgery, chemotherapy, and radiotherapy, the life expectancy of the patient with glioblastoma is approximately 11 months. To enhance glioma-specific gene...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/1043034041648372
更新日期:2004-08-01 00:00:00
abstract::As efficient and less toxic virus-derived gene therapy vectors are developed, a pressing problem is to avoid immune response to the therapeutic gene product. Secreted therapeutic proteins potentially represent a special problem, as they are readily available to professional antigen-presenting cells throughout the body...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.036
更新日期:2007-12-01 00:00:00
abstract::Direct arterial gene transfer has been previously achieved using double-balloon catheters and perforated balloons, in most cases facilitated by the use of cationic liposomes or viral vectors. These gene delivery systems, however, have been compromised by issues relating to efficacy and/or safety, and furthermore requi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1993.4.6-749
更新日期:1993-12-01 00:00:00
abstract::C-C chemokine receptor type 5 (CCR5) is a major co-receptor for the entry of human immunodeficiency virus type-1 (HIV-1) into target cells. Human hematopoietic stem cells (hHSCs) with naturally occurring CCR5 deletions (Δ32) or artificially disrupted CCR5 have shown potential for curing acquired immunodeficiency syndr...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.126
更新日期:2012-02-01 00:00:00
abstract::Targeted delivery of intravenously administered genetically altered cells or stem cells is still in an early stage of investigation. We developed a method of delivering iron oxide (ferumoxide)-labeled mesenchymal stem cells (MSCs) to a targeted area in an animal model by applying an external magnet. Rats with or witho...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303404322959506
更新日期:2004-04-01 00:00:00
abstract::Virotherapy is a unique modality for the treatment of cancer with oncolytic viruses (OVs) that selectively infect and lyse tumor cells, spread within tumors, and activate anti-tumor immunity. Various viruses are being developed as OVs preclinically and clinically, several of them engineered to encode therapeutic prote...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
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更新日期:2017-10-01 00:00:00
abstract::The use of nonionic polymeric micelles orally to protect and deliver plasmid DNA in vivo was investigated. Parathyroid hormone (PTH)(1-34) gene (179 bp) was inserted into a human cytomegalovirus promoter (PCMV) and E. coli competent cells were used to amplify the cDNA. Polymeric micelle formations (100 microl) formed ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.015
更新日期:2009-11-01 00:00:00
abstract::Spinal muscular atrophy (SMA) is an autosomal recessive disease affecting ∼1 in 10,000 live births. The most striking component is the loss of α-motor neurons in the ventral horn of the spinal cord, resulting in progressive paralysis and eventually premature death. There is no current treatment paradigm other than sup...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2012.225
更新日期:2013-05-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2016.071
更新日期:2016-06-01 00:00:00
abstract::Reporter gene-based molecular imaging can provide invaluable information on the fate of cellular therapies postimplantation. Integrating lentiviral vectors (ILVs) are commonly used for stably engineering cells; however, their potential for insertional mutagenesis poses a significant safety concern and barrier to wides...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.111
更新日期:2018-10-01 00:00:00
abstract::Lentiviral vectors hold great promise for the genetic correction of various inherited diseases. However, lentiviral vector biology is still not completely understood and warrants the precise decoding of molecular mechanisms underlying integration and post-translational modification. This study investigated a series of...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2017.162
更新日期:2017-10-01 00:00:00
abstract::Subcutaneous vaccination therapy with glioma cells, which are retrovirally transduced to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF), has previously proven effective in C57BL/6 mice harboring intracerebral GL261 gliomas. However, clinical ex vivo gene therapy for human gliomas would be difficult,...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050057503
更新日期:2000-07-01 00:00:00
abstract::Malignant pleural mesothelioma (MPM) is a fatal disease with a median survival of less than 14 months. For the first time, a genetically engineered vaccinia virus is shown to produce efficient infection, replication, and oncolytic effect against MPM. GLV-1h68 is a replication-competent engineered vaccinia virus carryi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2008.036
更新日期:2008-08-01 00:00:00
abstract::To target expression of toxic genes to Epstein-Barr virus (EBV)-associated tumor cells, we have developed an EBV-driven enzyme prodrug system (EDEPS) that takes advantage of the trans-activating properties of EBNA1, a latent protein expressed in all EBV-containing cells, to direct expression of cytosine deaminase (CD)...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.5-647
更新日期:1996-03-20 00:00:00
abstract::Vectors based on lentiviruses have become potent tools for efficient gene transfer to multiple cell types both in vitro and in vivo. In part this is attributable to the stability of transduction afforded by integration into the target cell genome. However, evidence indicates that episomal forms of the vector can also ...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2007.013
更新日期:2007-06-01 00:00:00
abstract::Stem cell mobilization to injured tissue contributes to neovascularization, resulting in regeneration after myocardial infarction (MI). We previously showed that direct cardiac injection of a recombinant lentivirus (LV) that engineers expression of membrane-bound stem cell factor (mSCF) improves outcomes immediately a...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2012.063
更新日期:2012-12-01 00:00:00