Abstract:
:Recombinant adeno-associated virus (AAV)-based vectors expressing therapeutic gene products have shown great potential for human gene therapy. One major challenge for translation of promising research to clinical development is the manufacture of sufficient quantities of AAV vectors that meet stringent standards for purity, potency, and safety required for human parenteral administration. Several methods have been developed to generate recombinant AAV in cell culture, each offering distinct advantages. Transient transfection-based methods for vector production are reviewed here, with a focus on specific considerations for development of AAV vectors as clinical products.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Wright JFdoi
10.1089/hum.2009.064subject
Has Abstractpub_date
2009-07-01 00:00:00pages
698-706issue
7eissn
1043-0342issn
1557-7422journal_volume
20pub_type
杂志文章,评审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
更新日期:2001-06-10 00:00:00
abstract::Classical gene therapy for cystic fibrosis has had limited success because of immune response against viral vectors and short-term expression of cDNA-based transgenes. These limitations could be overcome by delivering the complete genomic CFTR gene on nonintegrating human artificial chromosomes (HACs). Here, we report...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.225
更新日期:2010-09-01 00:00:00
abstract::In previous studies we demonstrated that a modified human HSP70b promoter (HSE.70b) directs high levels of gene expression to tumor cells after mild hyperthermia treatment in the range of 41.5-44 degrees C. This transcriptional targeting system exhibits low basal activity at 37 degrees C, is highly induced (950-fold) ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303403321467216
更新日期:2003-03-20 00:00:00
abstract::Tumor angiogenesis is a rate-limiting factor for tumor growth, and the endothelial cells of tumor vessels display specific features that can be exploited for the selective delivery of cancer therapeutics. To specifically target exogenous genes to angiogenic tumor vessels, we generated a panel of vesicular stomatitis v...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303403322168028
更新日期:2003-08-10 00:00:00
abstract::Naked plasmid DNA electrotransfer offers advantages over viral-based gene delivery, including being regulatory permissive, but factors influencing expression efficiency and cell fate impact on translational utility. This study compared co-expression of red and green fluorescence reporter plasmids with differing promot...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.062
更新日期:2019-02-01 00:00:00
abstract::Gene-modified lymphocytes have a potential role in the therapy of cancer, infectious diseases, and genetic disorders of the immune system. Current gene therapy protocols involving gene transfer into lymphocytes utilize retroviruses with amphotropic envelope proteins. However, transduction efficiencies in lymphocytes u...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.12-1415
更新日期:1996-08-01 00:00:00
abstract::Gene transfer of the herpes simplex virus thymidine kinase (TK) gene associated with ganciclovir (GCV) treatment can lead to death of TK-expressing cells, and of neighboring TK- cells because of the bystander effect. Thus, a small proportion of TK+ cells in a tumor can lead to its complete regression after GCV treatme...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050083298
更新日期:2000-07-20 00:00:00
abstract::A phase I clinical trial was conducted in which recombinant adenovirus containing the cystic fibrosis trans-membrane regulator (CFTR) (Ad2/CFTR) was administered by bronchoscopic instillation or aerosolization to the lungs of cystic fibrosis (CF) patients. In this paper, we evaluate the efficiency of Ad2/CFTR-mediated...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1089/104303401750298544
更新日期:2001-07-20 00:00:00
abstract::Ornithine transcarbamylase deficiency (OTCD) is an inborn error of urea synthesis that has been considered as a model for liver-directed gene therapy. Current treatment has failed to avert a high mortality or morbidity from hyperammonemic coma. Restoration of enzyme activity in the liver should suffice to normalize me...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340152712719
更新日期:2002-01-01 00:00:00
abstract::This multicenter phase I/II study evaluated the safety, pharmacokinetics, and antitumor effects of repeated doses of NV1020, a genetically engineered oncolytic herpes simplex virus, in patients with advanced metastatic colorectal cancer (mCRC). Patients with liver-dominant mCRC received four fixed NV1020 doses via wee...
journal_title:Human gene therapy
pub_type: 杂志文章,多中心研究
doi:10.1089/hum.2010.020
更新日期:2010-09-01 00:00:00
abstract::Guidelines for testing gene therapy products for ecotropic replication-competent retrovirus (Eco-RCR) have not been delineated as they have for amphotropic viruses. To evaluate biologic assays that can detect these viruses, we compared an S(+)/L(-) assay and a marker rescue assay designed specifically for Eco-RCR dete...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303402760293619
更新日期:2002-09-20 00:00:00
abstract::Recombinant adeno-associated virus serotype 2 (rAAV2)-based human gene therapy for cystic fibrosis has progressed through a series of preclinical studies and phase I and II clinical trials. This agent has shown an encouraging safety profile, consistent levels of DNA transfer, and positive evidence of short-term clinic...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章
doi:10.1089/hum.2005.16.921
更新日期:2005-08-01 00:00:00
abstract::The optimal stem cell source for stem cell gene therapy has not been defined. Most gene transfer studies have used peripheral blood or marrow repopulating cells collected after administration of granulocyte colony-stimulating factor and stem cell factor (G-CSF/SCF). For clinical applications, however, growth factor ad...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303403322542329
更新日期:2003-11-20 00:00:00
abstract::Adeno-associated viral (AAV) vectors are becoming increasingly popular in basic research as well as in clinical gene therapy. Due to its exceptional resistance against physical and chemical stress, however, the increasing use of AAV in laboratories and clinics around the globe raises safety concerns. Proper decontamin...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.120
更新日期:2020-11-06 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::To achieve effective gene therapy, it is necessary to selectively and efficiently transfect therapeutic gene into targeted cells. In this study, we developed a combination method using mannosylated lipoplexes, which show selectivity to antigen-presenting cells such as macrophages and dendritic cells, and bubble liposo...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.106
更新日期:2010-01-01 00:00:00
abstract::To develop a potential gene therapy strategy for the treatment of hemophilia A, we constructed several retroviral vectors expressing a B-domain-deleted factor VIII (FVIII) cDNA. We confirmed previous reports that when the FVIII cDNA is inserted into a retroviral vector, the vector mRNA is decreased resulting in signif...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1995.6.11-1363
更新日期:1995-11-01 00:00:00
abstract::Development of multidrug resistance (MDR) is the major obstacle to successful cancer chemotherapy. We have developed Daudi human lymphoma cells that are 20-fold more resistant than the parent cell line to vincristine (VCR) by infecting cells with pHaMDR1/A retroviral vector (Daudi/MDR20). Three DNA sequences of anti-M...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950018175
更新日期:1999-05-01 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
更新日期:1999-06-10 00:00:00
abstract::Mucopolysaccharidosis type II (MPS II) is a neuropathic lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase (IDS), which leads to the accumulation of glycosaminoglycans (GAGs). We demonstrated that biochemical alterations in the brains of MPS II mice are not corrected by bone marrow transplantat...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2014.158
更新日期:2015-06-01 00:00:00
abstract::Adeno-associated viral (AAV) vectors containing cone-specific promoters have rescued cone photoreceptor function in mouse and dog models of achromatopsia, but cone-specific promoters have not been optimized for use in primates. Using AAV vectors administered by subretinal injection, we evaluated a series of promoters ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2015.130
更新日期:2016-01-01 00:00:00
abstract::Gene electrotransfer is gaining momentum as an efficient methodology for nonviral gene transfer. In skeletal muscle, data suggest that electric pulses play two roles: structurally permeabilizing the muscle fibers and electrophoretically supporting the migration of DNA toward or across the permeabilized membrane. To in...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hgt.2008.060
更新日期:2008-11-01 00:00:00
abstract::Somatic gene therapy for pulmonary diseases must be accomplished in vivo, requiring the spread of a gene transfer vector across a vast expanse of respiratory epithelium. Surfactant, a naturally occurring protein and lipid mixture used to treat the respiratory distress syndrome of prematurity, disperses rapidly and eve...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.2-171
更新日期:1997-01-20 00:00:00
abstract::The purpose of this study was to assess the therapeutic potential of injecting the gene for HLA-B7/beta2-microglobulin into the subcutaneous metastatic nodules of patients who are refractory to conventional treatments. The nine patients evaluated were divided into three groups and given escalating doses of DNA (20, 40...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.14-2031
更新日期:1998-09-20 00:00:00
abstract::Recombinant adeno-associated virus 2 (rAAV) vectors have been successfully used for sustained expression of therapeutic genes. The potential of using rAAV as a cancer vaccine vector and the impact of a bacterial plasmid adjuvant on this activity were investigated. C57BL/6 mice received a single intramuscular injection...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2004.15.856
更新日期:2004-09-01 00:00:00
abstract::Oncolytic measles virus (MV) encoding the human thyroidal sodium iodide symporter (MV-NIS) has proved to be safe after intraperitoneal or intravenous administration in patients with ovarian cancer or multiple myeloma, respectively, but it has not yet been administered through intratumoral injection in humans. Squamous...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.128
更新日期:2012-03-01 00:00:00
abstract::DNA vaccination is an attractive approach for tumor immunotherapy because of its stability and simplicity of delivery. Advances demonstrate that helper T cell responses play a critical role in initiating immune responses. The aim of the current study is to test whether targeting HPV-16 E7 to the endosomal/lysosomal co...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950016474
更新日期:1999-11-20 00:00:00
abstract::Neurodegeneration in Parkinson's disease (PD) affects mainly dopaminergic neurons in the substantia nigra, where age-related, increasing percentages of cells lose detectable respiratory activity associated with depletion of intact mitochondrial DNA (mtDNA). Replenishment of mtDNA might improve neuronal bioenergetic fu...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.023
更新日期:2009-08-01 00:00:00
abstract::Adenoviruses are attractive vectors for gene transfer into cardiac muscle. However, their promiscuous tissue tropism, which leads to an ectopic expression of the transgene, is a considerable limitation. To restrict expression to cardiomyocytes, we have constructed two recombinant adenoviruses (Ad-MLC2-250betagal and A...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.13-1919
更新日期:1998-09-01 00:00:00
abstract::Lentiviral vectors are efficient gene delivery vehicles for therapeutic and research applications. In contrast to oncoretroviral vectors, they are able to infect most nonproliferating cells. In the liver, induction of cell proliferation dramatically improved hepatocyte transduction using all types of retroviral vector...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.227
更新日期:2013-02-01 00:00:00