Abstract:
:Replication-deficient retroviruses have been successfully utilized as vectors, offering an efficient, stable method of therapeutic gene delivery. Many examples exist proving this mode of integrative gene transfer is both effective and safe in cultured systems and clinical trials. Along with their success, severe side effects have occurred with early retroviral vectors causing a shift in the approach to vector design before further clinical testing. Several alternative delivery methods are available but lentiviral vectors (LV) are among the most favorable as they are already well understood. LV offer safer integration site selection profiles and a lower degree of genotoxicity, compared with γ-retroviral vectors. Following their introduction, development of the self-inactivating vector configuration was a huge step to this mode of therapy but did not confer full protection against insertional mutagenesis. As a result integration, modeling must be improved to eventually avoid this possibility. The cellular factor LEDGF/p75 seems to play an essential role in the process of LV site selection and its interactions with chromatin are being quickly resolved. LEDGF/p75 is at the center of one example directed integration effort where recombinant products bias the integration event, a step toward fully directed integration into pre-determined benign loci. A more accurate picture of the details of LEDGF/p75 in the natural integration process is emerging, including new binding specificities, chromatin interaction kinetics and additional cellular factors. Together with next-generation sequencing technology and bio-informatics to analyze integration patterns, these advancements will lead to highly focused directed integration, accelerating wide-spread acceptance of LV for gene therapy.
journal_name
Gene Therjournal_title
Gene therapyauthors
Papayannakos C,Daniel Rdoi
10.1038/gt.2012.88subject
Has Abstractpub_date
2013-06-01 00:00:00pages
581-8issue
6eissn
0969-7128issn
1476-5462pii
gt201288journal_volume
20pub_type
杂志文章,评审相关文献
GENE THERAPY文献大全abstract::Gene transfer complexes containing poly-L-lysine (poly-K) and DNA with ligands directed at the serpin enzyme complex receptor (sec-R) deliver reporter genes to receptor-bearing cells in vivo. Expression lasts for about 30 days, when complexes containing long-chain poly-K are used. Extending the duration of expression ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302299
更新日期:2004-09-01 00:00:00
abstract::Sustainable correction of severe human genetic disorders of self-renewing tissues, such as the blistering skin disease junctional epidermolysis bullosa (JEB), is facilitated by stable genomic integration of therapeutic genes into somatic tissue stem cells. While integrating viral vectors can achieve this, they suffer ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301978
更新日期:2003-07-01 00:00:00
abstract::Intracardiac gene transfer and gene therapy have been investigated with different vector systems. Here we used adeno-associated virus (AAV) vectors to deliver either a reporter gene or a therapeutic gene into the heart of golden Syrian hamsters. The method of gene delivery was direct infusion of the AAV2 vectors into ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302078
更新日期:2003-10-01 00:00:00
abstract::Chronic infection with hepatitis B virus (HBV) puts individuals at high risk for complicating cirrhosis and liver cancer, but available treatment to counter the virus rarely eliminates infection. Although harnessing RNA interference (RNAi) to silence HBV genes has shown the potential, achieving efficient and durable s...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2014.94
更新日期:2015-02-01 00:00:00
abstract::The structure of 'stabilized plasmid-lipid particles' (SPLP) and their properties as systemic gene therapy vectors has been investigated. We show that SPLP can be visualized employing cryo-electron microscopy to be homogeneous particles of diameter 72 +/- 5 nm consisting of a lipid bilayer surrounding a core of plasmi...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301308
更新日期:2000-11-01 00:00:00
abstract::Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) promotes soft tissue and bone healing, and is Food and Drug Administration-approved for treatment of diabetic ulcers and periodontal defects. The short half-life of topical rhPDGF-BB protein application necessitates bolus, high-dose delivery. Gene therapy...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2016.73
更新日期:2017-01-01 00:00:00
abstract::Phase 1 clinical trials of liposome-mediated gene therapy for cystic fibrosis have been completed and in all cases the expression level achieved has been low and transient. Clearly, improvements in the efficiency of gene transfer are required. It is now being recognised that delivery of high doses of DNA/liposomes to ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301097
更新日期:2000-03-01 00:00:00
abstract::T-cell dysfunction is thought to be central to the immunodeficiency state seen in patients with the Wiskott-Aldrich syndrome (WAS). Aspects of the WAS phenotype have been corrected in other cell types on introduction of the normal WAS protein (WASP), but the potential for correction of the T-cell defects has not been ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301950
更新日期:2003-05-01 00:00:00
abstract::The E1 deleted adenoviral vectors are efficient at gene transfer to cells in culture or in animals. However, their use is limited because of an immune-mediated loss of transduced cells. This immune response is believed to result from low-level production of viral antigens from these vectors after gene transfer. The ea...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1995-06-01 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::The majority of immunotherapy-based gene therapy protocols consist of ex vivo gene transfer in tumor cells. To prevent further in vivo growth, modified cells must be irradiated before reinjection into patients. The present study examines the effects of gamma-irradiation on transgene expression in transduced leukemic c...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301870
更新日期:2003-02-01 00:00:00
abstract::Soluble receptors to vascular endothelial growth factor (VEGF) can inhibit its angiogenic effect. Since angiogenesis is involved in wound repair, we hypothesized that adenovirus-mediated gene transfer of a soluble form of VEGF receptor 2 (Flk-1) would attenuate wound healing in mice. C57Bl/6J and genetically diabetic ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302162
更新日期:2004-02-01 00:00:00
abstract::Intracerebral administration of recombinant adeno-associated vector (AAV) has been performed in several clinical trials. However, delivery into the brain requires multiple injections and is not efficient to target the spinal cord, thus limiting its applications. To assess widespread and less invasive strategies, we te...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2014.121
更新日期:2015-04-01 00:00:00
abstract::Low levels of expression in haemopoietic cells of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (A Tase), is associated with the dose-limiting sensitivity of these cells to the chemotherapeutic chloroethylating and related methylating agents. Thus, the use of agents which deplete ATase such as O6-benzylg...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::Delivery of a normal copy of CFTR cDNA to airway epithelia may provide a novel treatment for cystic fibrosis lung disease. Unfortunately, current vectors are inefficient because of limited binding to the apical surface of airway epithelia. We recently reported that incorporation of adenovirus in a calcium phosphate co...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301020
更新日期:1999-11-01 00:00:00
abstract::To test whether fast-acting, self-complimentary (sc), adeno-associated virus-mediated RPE65 expression prevents cone degeneration and/or restores cone function, we studied two mouse lines: the Rpe65-deficient rd12 mouse and the Rpe65-deficient, rhodopsin null ('that is, cone function-only') Rpe65(-/-)::Rho(-/-) mouse....
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.29
更新日期:2010-07-01 00:00:00
abstract::For certain gene therapy applications, the simultaneous delivery of multiple genes would allow for novel therapies. In the case of adeno-associated virus (AAV) vectors, the limited packaging capacity greatly restricts current methods of carrying multiple transgene cassettes. To address this issue, a recombinant AAV (r...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.106
更新日期:2009-11-01 00:00:00
abstract::We have compared the efficacy of daily injection of recombinant leptin protein (rh-leptin) with adenovirus-mediated delivery of the murine or human leptin gene (Ad-leptin) for treatment of obesity in the obese (ob/ob) mouse model. We demonstrate an improved correction profile for obesity and associated surrogate marke...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300565
更新日期:1998-01-01 00:00:00
abstract::Selection of targeted vectors from virus display peptide libraries is a versatile and efficient approach to improve vector specificity and efficiency. This strategy has been used to target various cell types in vitro. Here, we report the screening of an adeno-associated virus type 2 (AAV2) display peptide library in v...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.44
更新日期:2010-08-01 00:00:00
abstract::Human adipose tissue mesenchymal stromal cells (AMSCs) share common traits, including similar differentiation potential and cell surface markers, with their bone marrow counterparts. Owing to their general availability, higher abundance and ease of isolation AMSCs may be convenient autologous delivery vehicles for loc...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2008.176
更新日期:2009-04-01 00:00:00
abstract::Gene therapy is thought to be a promising method for the treatment of various diseases. One gene therapy strategy involves the manipulations on a process of formation of new vessels, commonly defined as angiogenesis. Angiogenic and antiangiogenic gene therapy is a new therapeutic approach to the treatment of cardiovas...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302621
更新日期:2005-10-01 00:00:00
abstract::p53 gene therapy is being tested clinically for the treatment of human cancer, however, some cancer models (in vivo and in vitro) are resistant to p53. To explore the potential use of two p53 homologues, p73 and p51/p63, in cancer gene therapy, we introduced p53, p73 and p51/p63 into colorectal cancer cell lines via a...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301538
更新日期:2001-09-01 00:00:00
abstract::Direct gene transfer for the treatment of human diseases requires a vector which can be administered efficiently, safely and repeatedly. Cationic liposomes represent one of the few examples that can meet these requirements. Currently, more than a dozen cationic liposome formulations have been reported. These liposomes...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:
更新日期:1995-12-01 00:00:00
abstract::In the last two decades, remarkable advances have been made in the development of technologies used to engineer new aptamers and ribozymes. This has encouraged interest among researchers who seek to create new types of gene-control systems that can be made to respond specifically to small-molecule signals. Validation ...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/gt.2009.81
更新日期:2009-10-01 00:00:00
abstract::Cytomegalovirus (CMV) promoter is often present in recombinant adenovirus vectors (AdVs) suitable for gene therapy, ensuring high levels of transgene production in a wide range of hosts. Despite this characteristic, the presence of the AdV genome in target cells and tissues typically lasts longer than transgene produc...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301296
更新日期:2000-10-01 00:00:00
abstract::The failure of pharmacological approaches to cure infection with the human immunodeficiency virus (HIV) has renewed the interest in gene-based therapies. Among the various strategies that are currently explored, the blockade of HIV entry into susceptible T cells and macrophages promises to be the most powerful interve...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302755
更新日期:2006-07-01 00:00:00
abstract::Plasmids carrying the Epstein-Barr virus (EBV) latent gene EBNA1 and the EBV latent origin of replication (oriP) stay in transfected human cells as autonomously replicating extrachromosomal genetic units. They thus might represent a suitable tool for cytokine gene introduction into human tumor cells with the prospect ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300363
更新日期:1997-02-01 00:00:00
abstract::The broad host cell range and high expression levels of transgenes are features that have made alphaviruses attractive for gene expression studies and gene therapy applications. Particularly, Semliki Forest virus vectors have been applied for large-scale production of recombinant membrane proteins for drug screening p...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302620
更新日期:2005-10-01 00:00:00
abstract::We created Na(+)/HCO3(-) cotransporter 1 (NBCe1) p.W516* knock-in mice as a model of isolated proximal renal tubular acidosis showing early lethality associated with severe metabolic acidosis to investigate the therapeutic effects of prenatal alkalization or posttranscriptional control 124 (PTC124). NBCe1(W516*/W516*)...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2015.7
更新日期:2015-05-01 00:00:00
abstract::The development of efficient systems for in vivo gene transfer to the central nervous system (CNS) may provide a useful therapeutic strategy for the alleviation of several neurological disorders. In this study, we evaluated the feasibility of nonviral gene therapy to the CNS mediated by cationic liposomes. We present ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302516
更新日期:2005-08-01 00:00:00