Abstract:
:The successful development of adenovirus vectors for vaccines and gene therapy will require a better understanding of the host immune response. Using the ELISPOT assay to measure IFN-gamma-secreting CD8(+) cells, we identify immunodominant epitopes of the adenovirus hexon and DNA-binding protein in BALB/c and C57BL/6 mice. The T-cell response to the intramuscular administration of adenovirus serotype 5 peaks within a few weeks and gradually declines but is still detectable after 12 weeks. A second administration did not substantially increase the number of reactive T cells. The CD8(+) T-cell response was also similar between wild type and E1-deleted adenovirus. When B-cell-deficient mice were injected with adenovirus encoding the gene for secreted alkaline phosphatase, sera phosphatase activity was reduced more quickly in mice pre-exposed to adenovirus. These results add to the evidence that cell-mediated immunity is a substantial barrier to therapeutic adenoviral vectors and provide more quantitative tools to measure cellular immune responses to adenovirus.
journal_name
Gene Therjournal_title
Gene therapyauthors
McKelvey T,Tang A,Bett AJ,Casimiro DR,Chastain Mdoi
10.1038/sj.gt.3302232keywords:
subject
Has Abstractpub_date
2004-05-01 00:00:00pages
791-6issue
9eissn
0969-7128issn
1476-5462pii
3302232journal_volume
11pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract::The prognosis of pancreatic adenocarcinoma is poor and current treatment ineffective. A novel treatment strategy is described here using a mouse model system for pancreatic cancer. Cells that have been genetically modified to express the cytochrome P450 2B1 enzyme are encapsulated in cellulose sulphate and implanted i...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300671
更新日期:1998-08-01 00:00:00
abstract::We previously demonstrated that recombinant adeno-associated virus vectors based on serotype 2 (rAAV2) can direct transgene expression in salivary gland cells in vitro and in vivo. However, it is not known how other rAAV serotypes perform when infused into salivary glands. The capsids of serotypes 4 and 5 are distinct...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302691
更新日期:2006-04-01 00:00:00
abstract::Current tools for the inhibition of microRNA (miR) function are limited to modified antisense oligonucleotides, sponges and decoy RNA molecules and none have been used to understand miR function during development. CRISPR/Cas-mediated deletion of miR sequences within the genome requires multiple chromosomal deletions ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2016.22
更新日期:2016-06-01 00:00:00
abstract::Tissue-specific promoters for gene therapy are typically too big for adeno-associated virus (AAV) vectors; thus, the exploration of small effective non-viral regulatory elements is of particular interest. Wild-type AAV can specifically integrate into a region on human chromosome 19 termed AAVS1. Earlier work has deter...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2008.134
更新日期:2009-01-01 00:00:00
abstract::In muscle, mutant genes can be targeted and corrected directly by intramuscular (i.m.) injection of corrective DNA, or by ex vivo delivery of DNA to myogenic cells, followed by cell transplantation. Short fragment homologous replacement (SFHR) has been used to repair the exon 23 nonsense transition at the Xp21.1 dys l...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301737
更新日期:2002-06-01 00:00:00
abstract::Glucagon-like peptide-1 (GLP-1) is an incretin hormone that performs a wide array of well-characterized antidiabetic actions, including stimulation of glucose-dependent insulin secretion, upregulation of insulin gene expression and improvements in beta-cell survival. GLP-1-receptor agonists have been developed for tre...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.143
更新日期:2010-02-01 00:00:00
abstract::Recombinant adenoviruses (Ad) are attractive vectors for gene transfer in vitro and in vivo. However, the widely used E1-deleted vectors as well as newer generation vectors contain viral sequences, including transcriptional elements for viral gene expression. These viral regulatory elements can interfere with heterolo...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301139
更新日期:2000-04-01 00:00:00
abstract::Mutations in GJB2, which codes for the gap junction (GJ) protein connexin26 (Cx26), are the most common causes of human nonsyndromic hereditary deafness. We inoculated modified adeno-associated viral (AAV) vectors into the scala media of early postnatal conditional Gjb2 knockout mice to drive exogenous Cx26 expression...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2013.59
更新日期:2014-01-01 00:00:00
abstract::Apo(a) is a very atherogenic plasma protein without apparent function, which is highly expressed in humans. The variation in plasma Lp(a) concentration among individuals is considerable. Approximately 10-15% of the white population exhibit plasma Lp(a) concentrations above the atherogenic cut-off value of approximatel...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301434
更新日期:2001-03-01 00:00:00
abstract::The development of lentiviral vectors that use Rev-independent mechanisms of nuclear export for their genomic RNA could facilitate the construction of novel anti-HIV vectors. We have improved the titers of Rev-independent lentiviral vectors having the SRV-1 CTE by mutating the major splice donor and acceptor sites pre...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301262
更新日期:2000-08-01 00:00:00
abstract::Production of retroviral vectors for clinical use requires removal of cells and cellular debris. We combined a series of filters of decreasing pore size using commercially available blood banking filters approved for clinical use. The collection bag and filters can be connected to create a sterile, closed system using...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301328
更新日期:2000-12-01 00:00:00
abstract::Human adenovirus (Ad) vectors are extensively used as gene transfer vehicles. However, a serious obstacle for the use of these vectors in clinical applications is due to pre-existing immunity to human Ads affecting the efficacy of gene transfer. One of the approaches to circumvent host immune response could be the dev...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302146
更新日期:2004-01-01 00:00:00
abstract::Various methods for determining the expression of the beta-galactosidase (beta-gal) gene after retroviral transduction were compared as a means to assess retroviral titre. To allow better comparison, different retroviral vectors were constructed carrying two mutants of the green fluorescent protein and assessed as sen...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300519
更新日期:1997-11-01 00:00:00
abstract::Retroviral vectors are being used increasingly in clinical gene therapy protocols but low transduction frequencies are presenting a significant obstacle to progress. In this paper we report a simple method to enhance the efficiency of ex vivo retroviral gene transfer. Calcium chloride is added to the vector stock and ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
abstract::We demonstrated previously that the additive-type recombinant Sendai virus (rSeV) is highly efficient for use in pulmonary gene transfer; however, rSeV exhibits inflammatory responses. To overcome this problem, we tested newly developed non-transmissible constructs, namely, temperature-sensitive F-deleted vector, rSeV...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302955
更新日期:2007-07-01 00:00:00
abstract::Replication defective viral vectors provide a potentially useful means of gene transfer to oligodendrocytes and thus for studying the pathogenesis of white matter disease. In this study we have examined the expression pattern of E1/E3 deleted adenoviral vectors expressing the reporter gene LacZ (AdlacZ) as a means of ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300971
更新日期:1999-08-01 00:00:00
abstract::Gene transfer to airway epithelia with amphotropic pseudotyped retroviral vectors is inefficient following apical vector application. To better understand this inefficiency, we localized the expression of Pit2, the amphotropic receptor, in polarized human airway epithelia. Pit2 was expressed on both the apical and bas...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301714
更新日期:2002-07-01 00:00:00
abstract::Hydrodynamic gene delivery is an attractive option for non-viral liver gene therapy, but requires evaluation of efficacy, safety and clinically applicable techniques in large animal models. We have evaluated retrograde delivery of DNA to the whole liver via the isolated segment of inferior vena cava (IVC) draining the...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3303079
更新日期:2008-03-01 00:00:00
abstract::Short hairpin RNA (shRNA)-mediated gene regulation is a commonly used technique for gene manipulation. An efficient and safe delivery system is indispensable when shRNA is delivered into living organisms for gene therapy. Previous studies have proved that DNA and protein can be delivered into dendritic cells (DCs) by ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2014.50
更新日期:2014-07-01 00:00:00
abstract::Parkinson's disease is a prevalent progressive degenerative disorder of the elderly. There is a current need for novel therapeutic strategies because the standard levodopa pharmacotherapy is only temporarily efficacious. Recently, there have been some high-profile successful preclinical results obtained in animal mode...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302669
更新日期:2006-03-01 00:00:00
abstract::HaCaT cells, a spontaneously immortalised, nontumorigenic keratinocyte line, were used as a more amenable model than primary keratinocytes for ex vivo-mediated gene transfer. These cells were transduced with retroviral vectors containing the factor IX cDNA under the control of a cytomegaloviral (CMV) promoter/enhancer...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300591
更新日期:1998-03-01 00:00:00
abstract::Constitutive expression of short hairpin RNAs (shRNAs) may cause cellular toxicity in vivo and using microRNA (miRNA) scaffolds can circumvent this problem. Previously, we have shown that embedding small interfering RNA sequences targeting apolipoprotein B100 (ApoB) in shRNA (shApoB) or miRNA (miApoB) scaffolds result...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2013.58
更新日期:2014-01-01 00:00:00
abstract::Glioblastoma multiforme (GBM) is one of the most formidable brain tumors with a mean survival period of approximately 12 months. To date, a combination of radiotherapy and chemotherapy with an oral alkylating agent, temozolomide (TMZ), has been used as first-line therapy for glioma. However, the efficacy of chemothera...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.88
更新日期:2010-11-01 00:00:00
abstract::The GM2-gangliosidoses are neurological diseases causing premature death, thus developing effective treatment protocols is urgent. GM2-gangliosidoses result from deficiency of a lysosomal enzyme β-hexosaminidase (Hex) and subsequent accumulation of GM2 gangliosides. Genetic changes in HEXA, encoding the Hex α subunit,...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/s41434-019-0120-5
更新日期:2020-05-01 00:00:00
abstract::Plasma apolipoprotein AI (apoAI) and lecithin-cholesterol acyltransferase (LCAT) play important roles in reverse cholesterol transport, promoting the removal of excess cholesterol from peripheral cells and reducing formation of atherosclerotic lesions. Gene augmentation of either apoAI or LCAT, or both, are thus attra...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300746
更新日期:1998-10-01 00:00:00
abstract::Radioiodide concentrating activity in the thyroid, mediated by human Na+/I- symporter (hNIS), provides a mechanism for effective radioiodide treatment for patients who have invasive, recurrent, and metastatic thyroid cancers after total thyroidectomy. In an attempt to develop hNIS gene transfer for radioiodide therapy...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301170
更新日期:2000-05-01 00:00:00
abstract::Isolated limb perfusion (ILP) is a limb salvage surgical modality used to deliver chemotherapy and biologic agents to locally advanced and recurrent extremity soft tissue sarcoma (STS), and may be readily tailored for delivery of gene therapy. We set out to test the feasibility of delivering AdFLAGp53 (replication inc...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302911
更新日期:2007-04-01 00:00:00
abstract::Glucagon-like peptide 1 (GLP-1) and its analogue exendin-4 (Ex4) have displayed potent glucose homeostasis-modulating characteristics in type 2 diabetes (T2D). However, there are few reports of effectiveness in type 1 diabetes (T1D) therapy, where there is massive loss of beta cells. We previously described a novel GL...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302944
更新日期:2007-06-01 00:00:00
abstract::A major concern of using viral gene therapy is the potential for uncontrolled vector propagation and infection that might result in serious deleterious effects. To enhance the safety, several viral vectors, including vectors based on Sindbis virus, were engineered to lose their capability to replicate and spread after...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2008.153
更新日期:2009-02-01 00:00:00
abstract::Efficient gene delivery is a critical obstacle for gene therapy that must be overcome. Until current limits of gene delivery technology are solved, identification of systems with bystander effects is highly desirable. As an anticancer agent, radioactive iodine (131)I has minimal toxicity. The physical characteristics ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302758
更新日期:2006-07-01 00:00:00