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 transduction of bronchial airway cells. The ability of an Ad2/CFTR vector to transduce airway cells was first evaluated in patients to whom the vector was administered by bronchoscopic instillation. Cells at the administration site were collected 2 days after treatment by bronchoscopic brushing. Ad2-specific CFTR DNA was detected in four of five individuals by PCR, and Ad2-specific CFTR RNA was detected in three of five individuals by RT-PCR. Ad2/CFTR-mediated transduction of airway epithelial cells was then determined in CF individuals receiving this vector by aerosol inhalation. Ad2-specific CFTR DNA was detected in 13 of 13 individuals 2 days after aerosolization, and in 3 of 5 individuals 7 days after aerosolization. Ad2-specific RNA was detected in 4 of 13 individuals on day 2, but was not detected in the 5 individuals tested on day 7. The percentage of airway epithelial cells containing nuclear-localized vector DNA was < or =2.4% as determined by fluorescence in situ hybridization (FISH). However, in some cases, a high percentage of nonepithelial mononuclear cells or squamous metaplastic epithelial cells was infected with the adenoviral vector. In conclusion, aerosol administration is a feasible means to distribute adenoviral vectors throughout the conducting airways, but improvements in adenovirus-mediated transduction of airway epithelial cells are necessary before gene therapy for CF will be effective.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Perricone MA,Morris JE,Pavelka K,Plog MS,O'Sullivan BP,Joseph PM,Dorkin H,Lapey A,Balfour R,Meeker DP,Smith AE,Wadsworth SC,St George JAdoi
10.1089/104303401750298544keywords:
subject
Has Abstractpub_date
2001-07-20 00:00:00pages
1383-94issue
11eissn
1043-0342issn
1557-7422journal_volume
12pub_type
临床试验,杂志文章,多中心研究abstract::The immunogenicity of adenovirus vectors remains a major obstacle to their safe and efficacious use for gene therapy. In order to identify T-cell epitopes directly from adenoviruses, four viral protein sequences were screened for the well-characterized 9-mer HLA-A2 binding motif. Peripheral blood mononuclear cells (PB...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303402320138952
更新日期:2002-07-01 00:00:00
abstract::Production of clinical-grade gammaretroviral vectors for ex vivo gene delivery requires a scalable process that can rapidly generate large amounts of vector supernatant, clear large numbers of residual packaging cells with minimal decreases in vector titer, and satisfy all current regulatory guidelines regarding produ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2010.064
更新日期:2011-01-01 00:00:00
abstract::One of the major obstacles to pulmonary-directed gene therapy using adenoviral vectors is the induction of inflammation. We investigated whether the adenoviral particles that constitute the initial inoculum can serve as an inflammatory stimulus, independent of their ability to express genes that they contain. Viral pa...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1995.6.12-1553
更新日期:1995-12-01 00:00:00
abstract::T lymphocytes, regardless of their specificity, are considered key targets for genetic modification in the treatment of inherited or acquired human diseases. In this study, we generated Lewis T cell lines specific for Dark Agouti rat alloantigens and tested the potential of allospecific T lymphocytes as carriers of ge...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050032401
更新日期:2000-06-10 00:00:00
abstract::Blood vessels are among the easiest targets for gene therapy. However, no data are available about the safety and feasibility of intracoronary gene transfer in humans. We studied the safety and efficacy of catheter-mediated vascular endothelial growth factor (VEGF) plasmid/liposome (P/L) gene transfer in human coronar...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2000-01-20 00:00:00
abstract::Defined serum-free conditions have great conceptual advantages for the biological safety and standardization of clinical gene transfer into hematopoietic stem cells. In the only study reported to date, Sekhar et al. achieved low serum conditions by a complex concentration procedure of a retroviral supernatant initiall...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.6-771
更新日期:1998-04-10 00:00:00
abstract::Transfer of a herpes simplex virus-derived thymidine kinase (HSV-tk) gene into brain tumor cells and subsequent ganciclovir (GCV) treatment has been shown by others to be an effective treatment in rats with intracerebrally inoculated 9L gliosarcomas. Mechanism of action and reproducibility are, however, still a matter...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.2-197
更新日期:1996-01-20 00:00:00
abstract::The enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) expressed by the parasite Trypanosoma brucei (Tb) can convert allopurinol, a purine analogue, to corresponding nucleotides with greater efficiency than its human homologue. We have developed a retroviral system that expresses the parasitic enzyme and te...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340152528165
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abstract::Adeno-associated virus (AAV) vector technology is rapidly advancing and becoming not only the leading vector platform in the field of gene therapy but also a useful tool for functional genomic studies of novel proteins. As most vectors utilize constitutive promoters, this results in transgene expression during product...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2019.249
更新日期:2020-10-01 00:00:00
abstract::Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC) offer great hope for in vitro modeling of Parkinson's disease (PD), as well as for designing cell-replacement therapies. To realize these opportunities, there is an urgent need to develop efficient protocols for the directed differentiation of...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.054
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abstract::The initial stages following the in vitro cytokine stimulation of human cord blood CD34+ cells overlap with the period when lentiviral gene transfer is typically performed. Single-cell transcriptional profiling and time-lapse microscopy were used to investigate how the vector-cell crosstalk impacts on the fate decisio...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2019.009
更新日期:2019-08-01 00:00:00
abstract::Immunologically sensitized recipients present one of the most critical problems in clinical organ transplantation today, since preformed antibodies rapidly destroy donor tissue expressing specific MHC class I antigens (Ag). Therefore, sensitized patients are either unable to receive a compatible organ, or experience a...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050015923
更新日期:2000-02-10 00:00:00
abstract::Retinal gene therapy based on adeno-associated viral (AAV) vectors is safe and efficient in humans. The low intrinsic DNA transfer capacity of AAV has been expanded by dual vectors where a large expression cassette is split in two halves independently packaged in two AAV vectors. Dual AAV transduction efficiency, howe...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2017.220
更新日期:2018-08-01 00:00:00
abstract::Replacement of the p53 tumor suppressor gene is a rational approach to the management of malignant gliomas because p53 is frequently mutated or inactivated in these cancers. Major weaknesses of this approach are that malignant gliomas are mixtures of cells with wild-type and mutant p53, and that tumor cells exhibiting...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2005.16.685
更新日期:2005-06-01 00:00:00
abstract::Point mutations in the dystrophin gene cause dystrophin deficiency and muscular dystrophy in the mdx mouse and a subset of patients with Duchenne muscular dystrophy. As an approach to gene therapy for muscular dystrophies due to point mutations, we have studied the ability of RNA-DNA chimeric oligonucleotides (chimera...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303402317322276
更新日期:2002-04-10 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1992.3.1-51
更新日期:1992-02-01 00:00:00
abstract::We studied hematopoietic progenitors from fetal baboon blood, marrow, and liver at four time points (125, 140, 160, and 175 days) during the third trimester (gestation approximately 180 days) to determine if fetal baboons might be an appropriate model for in utero gene therapy of hematopoietic stem cells (HSCs). Cells...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950018742
更新日期:1999-03-01 00:00:00
abstract::Kallistatin is a serine proteinase inhibitor that has been shown to reduce joint swelling and to inhibit inflammation in a rat model of arthritis. In this study, we investigated the effect and mechanisms of kallistatin on cardiac function after myocardial ischemia-reperfusion (I/R) injury. The human kallistatin gene i...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.1201
更新日期:2006-12-01 00:00:00
abstract::The efficient and specific introduction of genes into cancer cells in vivo remains a major challenge for current gene therapy modalities. Peptides possess appropriate properties to serve as tumor-targeting agents. Thus, finding new cancer-selective peptides directing gene transfer to neoplastic cells by reducing trans...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2005.16.1267
更新日期:2005-11-01 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::Adrenomedullin (AM) has been shown to protect against ischemia/reperfusion-induced myocardial infarction and apoptosis. In the present study, we examined the potential neuroprotective action of delayed AM gene transfer in cerebral ischemia. Three days after a 1-hr occlusion of the middle cerebral artery (MCAO), rats w...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2004.15.1243
更新日期:2004-12-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.3-325
更新日期:1998-02-10 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.9-1125
更新日期:1997-06-10 00:00:00
abstract::Foamy virus (FV) vectors are a promising gene delivery system for use in hematopoietic stem cell gene therapy. Previous FV vector marking studies in the NOD/SCID xenotransplantation model used umbilical cord blood (UCB)-derived SCID repopulating cells (SRCs) that were assayed 5-10 weeks posttransplantation. We now rep...
journal_title:Human gene therapy
pub_type: 杂志文章
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更新日期:2004-01-01 00:00:00
abstract::Accurate quantification of gene transfer (or gene correction) is a universal challenge in the field of gene therapy. In developing a clinical trial of lymphocyte gene therapy for Hunter syndrome (mucopolysaccharidosis type II), methods using Southern blot or automated DNA sequencing technology were employed, but found...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950016898
更新日期:1999-10-10 00:00:00
abstract::Therapeutic levels of expression of the beta-globin gene have been difficult to achieve with conventional retroviral vectors without the inclusion of DNase I-hypersensitive site (HS2, HS3, and HS4) enhancer elements. We generated recombinant adeno-associated viral (AAV) vectors carrying an antisickling human beta-glob...
journal_title:Human gene therapy
pub_type: 杂志文章
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更新日期:2008-04-01 00:00:00
abstract::Genetically modified lymphoblastoid cell lines (LCL) have been shown to be an attractive alternative source of antigen-presenting cells for cancer vaccination in vitro. We tested their application in patients with pancreatic cancer in a phase I clinical trial. As a model tumor antigen, we selected the point-mutated (c...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章
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更新日期:2012-12-01 00:00:00
abstract::Gyrate atrophy is a progressive blindness associated with deficiency of ornithine aminotransferase (OAT). The strategy of using an autologous keratinocyte graft, modified to express high levels of OAT as an ornithine-catabolizing skin-based enzyme sink, is investigated. Two OAT-containing retroviral vectors were const...
journal_title:Human gene therapy
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doi:10.1089/hum.1997.8.17-2125
更新日期:1997-11-20 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::This is an erratum of the published paper "Preclinical Evaluation of Chimeric Antigen Receptor-Modified T Cells Specific to Epithelial Cell Adhesion Molecule for Treating Colorectal Cancer". There are some errors in figure 6C and 7C in the article due to authors' mistakes when preparing the figures. Specifically, repr...
journal_title:Human gene therapy
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