Abstract:
:With the aim of developing new gene transfer tools for treating CF with gene therapy, we have synthesized a novel family of molecules named cationic phosphonolipids. The most efficient among them were selected by in vitro screening to compare their activities in vivo in mouse lungs. We used a reporter gene whose activity was measured cytofluorimetrically (FACS-Gal assay) and by means of a chemiluminescence technique. These tests allowed us to identify the percentage of transfected cells and to quantify total beta-galactosidase in the lungs. This enabled us to identify two molecules, significantly efficient in comparison with DNA alone: GLB73 (p = 0.0015) and GLB253 (p = 0.007). Their use resulted in a time lag between transfection and maximum efficiency: maximum efficiency was observed 4 days after transfection with GLB73, whereas it was noticeable only on day 7 with GLB253. Moreover, from toxicity studies carried out in vivo, GLB73 seems to be nontoxic. In vivo results were correlated with in vitro results obtained with CF epithelial cell lines. Consequently, GLB73 is a potential candidate for phase I clinical trials in humans.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Guillaume-Gable C,Floch V,Mercier B,Audrézet MP,Gobin E,Le Bolch G,Yaouanc JJ,Clément JC,des Abbayes H,Leroy JP,Morin V,Férec Cdoi
10.1089/hum.1998.9.16-2309subject
Has Abstractpub_date
1998-11-01 00:00:00pages
2309-19issue
16eissn
1043-0342issn
1557-7422journal_volume
9pub_type
杂志文章abstract::Dystrophic epidermolysis bullosa (DEB) comprises a family of inherited blistering skin disorders for which no corrective therapy currently exists. In the most severe form, the Hallopeau-Siemens subtype (RDEB-HS), the epidermal adhesion protein collagen VII is absent from the skin as a consequence of null mutations in ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340260201743
更新日期:2002-09-01 00:00:00
abstract::Combining chemotherapy and immunotherapy is problematic because chemotherapy can ablate the immune responses initiated by modulators of the immune system. We hypothesized that protection of immunocompetent cells from the toxic effects of chemotherapy, using drug resistance gene therapy strategies, would allow the comb...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.798
更新日期:2006-08-01 00:00:00
abstract::Cell encapsulation offers a safe and manufacturable method for the systemic delivery of therapeutic proteins from genetically engineered cells. However, control of dose delivery remains a major issue with regard to clinical application. We generated populations of immortalized murine NIH 3T3 fibroblasts that secrete m...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950018823
更新日期:1999-02-10 00:00:00
abstract::Liver ischemia-reperfusion (I/R) injury is a multifactorial process that affects graft function after liver transplantation. Inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-18, have been shown to play key roles in the pathophysiology of liver I/R injury. Studies have in...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2010.145
更新日期:2011-07-01 00:00:00
abstract::Lentiviral vectors are efficiently pseudotyped with RD114-TR, a chimeric envelope glycoprotein made of the extracellular and transmembrane domains of the feline leukemia virus RD114 and the cytoplasmic tail of the murine leukemia virus amphotropic envelope. RD114-TR-pseudotyped vectors may be concentrated by centrifug...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.138
更新日期:2007-09-01 00:00:00
abstract::Adenovirus vectors transduce liver hepatocytes with extreme efficiency; however, transgene expression is eliminated within 2 weeks. Extinction of transgene expression has been attributed to infiltrating cytotoxic T lymphocytes (CTLs) in the liver in a process that resembles a number of human diseases, including viral ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950019048
更新日期:1999-01-20 00:00:00
abstract::Current HIV-1 gene therapy approaches aim at stopping the viral life cycle at its earliest steps, such as entry or immediate postentry events. Among the most widely adopted strategies are CCR5 downregulation/knockout and the use of broadly neutralizing antibodies. However, the long-term efficacy and side effects are s...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2015.059
更新日期:2015-10-01 00:00:00
abstract::Clinical gene transfer research has involved adult and child subjects, and it is expected that gene transfer in fetal subjects will occur in the future. Some genetic diseases have serious adverse effects on the fetus before birth, and there is hope that prenatal gene therapy could prevent such disease progression. Res...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.062
更新日期:2011-11-01 00:00:00
abstract::Approaches to alter the native tropism of adenoviruses (Ads) are beneficial to increase their efficacy and safety profile. Liver tropism is important with regard to potential clinical toxicity in humans. Ad5/3 chimeras in which the Ad5 knob is substituted by the Ad3 knob, such as Ad5/3luc1, have been recently shown to...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340460745829
更新日期:2004-05-01 00:00:00
abstract::Genome engineering has gone mainstream because of breakthroughs in defining and harnessing naturally occurring, customizable DNA recognition cursors (protein or RNA-guided). At present, most gene editing relies on these cursors to direct custom DNA endonucleases to a specific genomic sequence to induce a double-strand...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2016.071
更新日期:2016-06-01 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
更新日期:2012-01-01 00:00:00
abstract::Advanced prostate cancer is invariably lethal once it becomes androgen independent (AI). With the aim of developing a new treatment we have used the human androgen-independent prostate cancer cell line, PC-3, to evaluate the effectiveness of two enzyme-directed prodrug therapy (EPT) systems as a novel means for promot...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.11-1617
更新日期:1998-07-20 00:00:00
abstract::The addition of replication-defective recombinant adenovirus to plasmid transfection (termed here "adenofection") has been shown to increase plasmid transgene expression in limited studies. Similarly, the addition of cationic liposomes to adenovirus increases adenovirus-mediated gene transduction (termed here "lipoduc...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950017059
更新日期:1999-09-20 00:00:00
abstract::Gene therapy has evolved into a tempting strategy for the management of cancer and other life-threatening diseases. Various approaches employ retroviral vectors to deliver the therapeutic gene. The profound knowledge about retrovirus biology allows the generation of increasingly advanced vector systems as well as an a...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2007.071
更新日期:2008-01-01 00:00:00
abstract::Sphingosine kinase 1 (SPK1) has been identified as a central mediator of ischemia preconditioning and plays a protective role in ischemia/reperfusion (I/R)-induced cardiomyocyte death. In the present study, we investigated the protective effect of adenovirus-mediated SPK1 gene (Ad-SPK1) transfer on I/R-induced cardiac...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2007.036
更新日期:2007-11-01 00:00:00
abstract::Mutations in the gene encoding the peroxisomal ATP-binding cassette transporter (ABCD1) cause elevations in very long-chain fatty acids (VLCFAs) and the neurodegenerative disease adrenoleukodystrophy (ALD). In most adults, this manifests as the spinal cord axonopathy adrenomyeloneuropathy (AMN). A challenge in virus-b...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.079
更新日期:2019-05-01 00:00:00
abstract::Gene-modified replication-competent adenoviruses (Ads) are emerging as a promising new modality for the treatment of cancer. We have previously shown that E1B 19kDa and E1B 55kDa gene-deleted Ad (Ad-DeltaE1B19/55) exhibits improved tumor-specific replication and cell lysis, leading to an enhanced antitumor effect. In ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.167
更新日期:2007-09-01 00:00:00
abstract::Targeted therapy produces objective responses in bladder cancer patients, although the responses can be short. Meanwhile, response rates to immune therapy are lower, but the effects are more durable. Based on these findings, it was hypothesized that urothelial carcinoma associated 1 (UCA1)-targeted therapy could syner...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.048
更新日期:2018-12-01 00:00:00
abstract::Hyperoxia and ischemia-reperfusion cause profound lung cellular damage mediated, in part, by generation of oxygen radicals. We hypothesized that gene therapy can be used to overcome oxidant injury by augmenting intracellular antioxidant enzymes. Adult rats were injected intratracheally with an adenovirus (Ad) vector e...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.10-1487
更新日期:1998-07-01 00:00:00
abstract::The objective of this phase II investigation is to assess the safety and efficacy of a plasmid mediated approach to induce angiogenesis/arteriogenesis with the angiomatrix protein Del-1 (developmentally regulated endothelial locus 1), in subjects with intermittent claudication (IC) secondary to peripheral arterial dis...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1089/104303404323142060
更新日期:2004-06-01 00:00:00
abstract::Activation of T cells is necessary for efficient retroviral-mediated gene transfer. In addition, if the population of infused cells is to be limited to transduced cells, a means of positive selection is required. We describe a clinical scale procedure for activation of donor T cells with anti-CD3/CD28 beads followed b...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340252939087
更新日期:2002-05-20 00:00:00
abstract::The transfer of a drug resistance gene into hematopoietic cells is an approach being investigated to overcome the problem of myelosuppression produced by anticancer drugs. Chemotherapeutic agents are often given in combination in order to increase their effectiveness. Consequently, there is an advantage in designing v...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.17-2537
更新日期:1998-11-20 00:00:00
abstract::C-C chemokine receptor type 5 (CCR5) is a major co-receptor for the entry of human immunodeficiency virus type-1 (HIV-1) into target cells. Human hematopoietic stem cells (hHSCs) with naturally occurring CCR5 deletions (Δ32) or artificially disrupted CCR5 have shown potential for curing acquired immunodeficiency syndr...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.126
更新日期:2012-02-01 00:00:00
abstract::Abstract Our studies have shown that coinjection of conventional single-stranded adeno-associated virus 2 (ssAAV2) vectors carrying the enhanced green fluorescent protein (EGFP) gene with self-complementary (sc) AAV2-T cell protein tyrosine phosphatase (TC-PTP) and scAAV2-protein phosphatase-5 (PP5) vectors resulted i...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.100
更新日期:2010-03-01 00:00:00
abstract::Administration of recombinant adenoviral (AdV) vectors to animals can lead to inflammatory and immune responses. For therapeutic indications in which repeated treatment is necessary, such as cystic fibrosis (CF), these responses can limit the therapeutic usefulness of the vector. In principle, the utility of the vecto...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401300042348
更新日期:2001-03-20 00:00:00
abstract::Delivery of plasmid DNA can be enhanced by treatment with ultrasound (US); acoustic cavitation appears to play an important role in the process. Ultrasound contrast agents (UCAs; stabilized microbubbles) nucleate acoustic cavitation, and lower the acoustic pressure threshold for inertial cavitation occurrence. Fifty m...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2005.16.893
更新日期:2005-07-01 00:00:00
abstract::Gene therapy studies in primates can provide important information regarding vector tropism, specific cellular expression, biodistribution, and safety prior to clinical trials. In this study, we report the assessment of transduction efficiency of recombinant adeno-associated virus (rAAV) vectors using human postmortem...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2010.157
更新日期:2011-05-01 00:00:00
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 p...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2009.064
更新日期:2009-07-01 00:00:00
abstract::An E1-, E2a-, E3-deleted adenoviral vector (Av3H82) encoding an epitope-tagged B domain-deleted human factor VIII cDNA (flagged FVIII) was evaluated in nonhuman primates. Twelve cynomolgus monkeys received intravenous administration of Av3H82; 6 monkeys received 6 x 10(11) particles/kg and another 6 received 3 x 10(12...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950016401
更新日期:1999-12-10 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