Abstract:
:Intravenous delivery of adenoviruses is the optimal route for many gene therapy applications. Once in the blood, coagulation factor X (FX) binds to the adenovirus capsid and protects the virion from natural antibody and classical complement-mediated neutralisation in mice. However, to date, no studies have examined the relevance of this FX/viral immune protective mechanism in human samples. In this study, we assessed the effects of blocking FX on adenovirus type 5 (Ad5) activity in the presence of human serum. FX prevented human IgM binding directly to the virus. In individual human sera samples (n=25), approximately half of those screened inhibited adenovirus transduction only when the Ad5-FX interaction was blocked, demonstrating that FX protected the virus from neutralising components in a large proportion of human sera. In contrast, the remainder of sera tested had no inhibitory effects on Ad5 transduction and FX armament was not required for effective gene transfer. In human sera in which FX had a protective role, Ad5 induced lower levels of complement activation in the presence of FX. We therefore demonstrate for the first time the importance of Ad-FX protection in human samples and highlight subject variability and species-specific differences as key considerations for adenoviral gene therapy.
journal_name
Gene Therjournal_title
Gene therapyauthors
Duffy MR,Doszpoly A,Turner G,Nicklin SA,Baker AHdoi
10.1038/gt.2016.32subject
Has Abstractpub_date
2016-07-01 00:00:00pages
592-6issue
7eissn
0969-7128issn
1476-5462pii
gt201632journal_volume
23pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract::The ability to restrict gene delivery and expression to particular cell types is of paramount importance for many types of gene therapy, especially in the lung. The alveolar epithelial type I (ATI) cell, in particular, is an attractive cell type to target, as it comprises 95% of the internal surface area of the lung. ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2016.52
更新日期:2016-10-01 00:00:00
abstract::We introduce a lung inflation-fixation protocol to examine the distribution and gene transfer efficiency of fluorescently tagged lipoplexes using fluorescence confocal microscopy within thick lung tissue sections. Using this technique, we tested the hypothesis that factors related to lipoplex distribution were the pre...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301461
更新日期:2001-06-01 00:00:00
abstract::Pancreatic cancer and chronic pancreatitis are clinical syndromes associated with severe pain that is difficult to manage. Thus, seeking additional pain reduction therapies is warranted. Excessive alcohol consumption over an extended period of time is the primary causal agent in pancreatitis. The efficacy of a replica...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/gt.2009.27
更新日期:2009-04-01 00:00:00
abstract::Citrullinemia is an autosomal recessive disorder caused by the deficiency of argininosuccinate synthetase (AS). It is characterized by elevated levels of blood citrulline and ammonia, which often results in hyperammonemic coma and early neonatal death in affected children. We have explored the use of adenoviral vector...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301303
更新日期:2000-10-01 00:00:00
abstract::We constructed a melanoma-specific oncolytic adenoviral vector Ad.MCDIRESE1.71Hsp3, in which the cytosine deaminase and adenoviral E1A genes linked by the IRES sequence were under the control of a mouse tyrosinase enhancer/promoter transcriptional element in the E1 region of the vector. We also inserted the human heat...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302776
更新日期:2006-08-01 00:00:00
abstract::As soon as RNA interference (RNAi) was found to work in mammalian cells, research quickly focused on harnessing this powerful endogenous and specific mechanism of gene silencing for human therapy. RNAi uses small RNAs, less than 30 nucleotides in length, to suppress expression of genes with complementary sequences. Tw...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302703
更新日期:2006-03-01 00:00:00
abstract::Hepatic sequestration of systemically administered adenoviral vectors reduces the number of viral particles available for delivery to other tissues. The biological basis of this phenomenon was investigated using a new in vivo technique which permitted imaging in real time. Recombinant adenovirus serotype 5 knob (Ad5K)...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300659
更新日期:1998-06-01 00:00:00
abstract::Newcastle disease virus (NDV) is an oncolytic paramyxovirus with a nonsegmented single-stranded RNA genome. In this report, a recombinant oncolytic NDV was passaged in human tumor xenografts and reisolated and characterized after two rounds of bioselection. Several isolates could be recovered that differed from the pa...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2012.13
更新日期:2013-01-01 00:00:00
abstract::First-generation adenoviral (Ad) vectors are frequently used vectors for experimental and clinical gene transfer. Earlier it has been shown that parallel overexpression of the cell cycle regulator p21(Waf1/Cip1) (p21) or antiapoptotic bcl-2 from a second vector reduces cytotoxicity and improves transgene expression. H...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.2
更新日期:2009-04-01 00:00:00
abstract::Intramuscular (i.m.) injection of plasmids followed by electropermeabilization is an efficient process to deliver genes into skeletal myofibers that permits proteins to be produced and secreted at therapeutically relevant levels. To further improve skeletal muscle as a bioreactor, we identified a formulation that elev...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301806
更新日期:2002-10-01 00:00:00
abstract::Angiogenesis plays a pivotal role in tumor growth, tissue invasion and metastasis. Endostatin is an angiogenesis inhibitor and has been shown to reduce tumor growth in animal models. However, therapy with recombinant endostatin protein was hampered by its short half-life and very-low yield of bioactive protein. We per...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3303038
更新日期:2008-02-01 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::Adenovirus vectors have great potential in cancer gene therapy. Targeting of cancer-testis (CT) antigens, which are specifically presented at the surface of tumor cells by human leukocyte antigen (HLA) class I molecules, is an attractive option. In this study, a single-chain T-cell receptor (scTCR) directed against th...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2008.26
更新日期:2008-07-01 00:00:00
abstract::An invasive Escherichia coli expressing the inv gene from Yersinia pseudotuberculosis was used as a vector for protein delivery to mammalian epithelial cells. Upon incubation with beta1-integrin-expressing mammalian cells, the bacteria are internalized, allowing bacteria-encoded proteins to function from within the ma...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302281
更新日期:2004-08-01 00:00:00
abstract::Choroidal neovascularization (CNV) leads to loss of vision in age-related macular degeneration (AMD), the leading cause of blindness in adult population over 50 years old. In this study, we developed intravenously administered, nanoparticulate, targeted nonviral retinal gene delivery systems for the management of CNV....
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2008.185
更新日期:2009-05-01 00:00:00
abstract::Cationic liposomes provide a means to introduce genes into cells both ex vivo and in vivo. In the past few years their use has been described in several tissues, e.g. lungs, liver, endothelium, brain. In this study we evaluated a commercially available poly-cationic liposome formulation in delivering a reporter gene i...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract::Hyperammonemia is less severe in arginase 1 deficiency compared with other urea cycle defects. Affected patients manifest hyperargininemia and infrequent episodes of hyperammonemia. Patients typically suffer from neurological impairment with cortical and pyramidal tract deterioration, spasticity, loss of ambulation, s...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2014.106
更新日期:2015-02-01 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::Many retroviral vectors based on murine leukaemia virus (MLV) contain the first 420 nucleotides of the gag gene, as this was reported to increase vector titre by increasing the efficiency of RNA packaging. In this study, deletion of this gag sequence from its original location did not decrease the titre of two retrovi...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301081
更新日期:2000-02-01 00:00:00
abstract::Sindbis virus expression has been used for in vitro investigations of antigen processing, presentation and epitope mapping. The recent development of a replication-deficient recombinant Sindbis virus expression vector has made in vivo expression possible with minimal pathogenic risk. Advantages of Sindbis virus over o...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300458
更新日期:1997-08-01 00:00:00
abstract::Morphine appears to be the most active metabolite of heroin; therefore, the effects of morphine are important in understanding the ramifications of heroin abuse. Opioid physical dependence (withdrawal response) may have very long-lasting effects on the motivation for reward, including the incubation of cue-induced dru...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2017.22
更新日期:2017-05-01 00:00:00
abstract::A replication-incompetent adenoviral vector encoding the heavy chain C-fragment (H(C)50) of botulinum neurotoxin type C (BoNT/C) was evaluated as a mucosal vaccine against botulism in a mouse model. Single intranasal inoculation of the adenoviral vector elicited a high level of H(C)50-specific IgG, IgG1 and IgG2a in s...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2008.181
更新日期:2009-03-01 00:00:00
abstract::Replication defective vectors derived from simple retroviruses or the more complex genomes of lentiviruses continue to offer the advantages of long-term expression, cell and tissue specific tropism, and large packaging capacity for the delivery of therapeutic genes. The occurrence of adverse events caused by insertion...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302570
更新日期:2005-07-01 00:00:00
abstract::We have previously synthesized a new cationic liposome that displays high efficiency and low toxicity, 3 beta[l-ornithinamide-carbamoyl] cholesterol (O-Chol), using solid-phase synthesis. In this study, O-Chol was applied to in vitro and in vivo models of ovarian cancer. Intraperitoneal gene delivery for peritoneal di...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301704
更新日期:2002-07-01 00:00:00
abstract::Adoptive cell therapy with chimeric antigen receptor (CAR)-modified T cells showed remarkable therapeutic efficacy in the treatment of leukaemia/lymphoma. However, the application to a variety of cancer entities is often constricted by the non-availability of a single chain antibody (scFv), which is usually the target...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2016.48
更新日期:2016-10-01 00:00:00
abstract::Green fluorescent protein (GFP) is a widely used intracellular reporter molecule to assess gene transfer and expression. A potential use for GFP is as a co-expressed marker, to select and enrich gene-modified cells by flow cytometry. Processed peptides derived from GFP and presented by the major histocompatibility com...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300951
更新日期:1999-07-01 00:00:00
abstract::Self-amplifying RNA (saRNA) is a promising biotherapeutic tool that has been used as a vaccine against both infectious diseases and cancer. saRNA has been shown to induce protein expression for up to 60 days and elicit immune responses with lower dosing than messenger RNA (mRNA). Because saRNA is a large (~9500 nt), n...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/s41434-019-0095-2
更新日期:2019-09-01 00:00:00
abstract::Gene therapy is an attractive method for the treatment of cardiovascular disease. However, using current strategies, induction of gene expression at therapeutic levels is often inefficient. In this study, we show a novel electroporation (EP) method to enhance the delivery of a plasmid expressing an angiogenic growth f...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.153
更新日期:2010-03-01 00:00:00
abstract::Multipotent adult progenitor cells (MAPCs) are bone marrow-derived stem cells with a high growth rate suitable for therapeutical applications as three-dimensional (3D) aggregates. Combined applications of osteogenically differentiated MAPC (OD-MAPC) aggregates and adeno-associated viral vectors (AAV) in bone bioengine...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2012.16
更新日期:2013-02-01 00:00:00
abstract::The proteasome is a multisubunit cytosolic protein complex responsible for degrading cytosolic proteins. Several studies have implicated its involvement in the processing of viral particles used for gene delivery, thereby limiting the efficiency of gene transfer. Peptide-based nonviral gene delivery systems are suffic...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302575
更新日期:2005-11-01 00:00:00