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 mouse erythropoietin (Epo) in response to stimulation by doxycycline or mifepristone. Engineered cells were introduced into AN69 hollow fibers, which were implanted in the peritoneal cavity or recipient mice. Animals receiving doxycycline or mifepristone showed stable polyhemia and increased serum Epo concentrations over a 6-month observation period, whereas animals not receiving the inducer drug had normal hematocrits. Epo secretion could be switched on and off, depending on the presence of doxycycline in the drinking water. In contrast, polyhemia was hardly reversible after subcutaneous injections of mifepristone. These data show that a permanent and regulated systemic delivery of a therapeutic protein can be obtained by the in vivo implantation of engineered allogeneic cells immunoprotected in membrane polymers.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Serguera C,Bohl D,Rolland E,Prevost P,Heard JMdoi
10.1089/10430349950018823keywords:
subject
Has Abstractpub_date
1999-02-10 00:00:00pages
375-83issue
3eissn
1043-0342issn
1557-7422journal_volume
10pub_type
杂志文章abstract::Adenoviruses (Ads) have shown great utility as vectors for the delivery of genes to mammalian cells, partly because of their ability to infect a wide range of different cell types independent of the replicative state of the cell. However, Ads do not transduce mature muscle efficiently because of low levels of the natu...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303404772679986
更新日期:2004-02-01 00:00:00
abstract::The recombinant adenoviral (Ad) vector is being considered as a cancer vaccine platform because it efficiently induces immune responses to tumor antigens by intradermal immunization. The aims of this study were to evaluate the potential toxicities and biodistribution after a single dose or six weekly intradermal doses...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.705
更新日期:2006-07-01 00:00:00
abstract::Fabry disease, caused by a deficiency of lysosomal enzyme alpha-galactosidase A (alpha-gal A), is one of the inherited disorders potentially treatable by gene transfer to hematopoietic stem cells. In this study, a high-titer amphotropic retroviral producer cell line, MFG-alpha-gal A, was established. CD34+ cells from ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950016302
更新日期:1999-12-10 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::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
更新日期:2001-09-01 00:00:00
abstract::Urocortin-2 (UCn2) peptide infusion increases cardiac function in patients with heart failure, but chronic peptide infusion is cumbersome, is costly, and provides only short-term benefits. Gene transfer would circumvent these shortcomings. We previously showed that a single intravenous (IV) injection of AAV8.UCn2 incr...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2014.157
更新日期:2015-06-01 00:00:00
abstract::We have shown that adenovirus-mediated manipulation of apoptotic genes such as bax could be a therapeutic option for prostate cancer. Unfortunately, the response of experimental prostate tumors to a single therapeutic gene of the apoptotic pathway is short-lived, and most of these tumors relapse after a short period o...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340260395901
更新日期:2002-11-20 00:00:00
abstract::Reporter gene-based molecular imaging can provide invaluable information on the fate of cellular therapies postimplantation. Integrating lentiviral vectors (ILVs) are commonly used for stably engineering cells; however, their potential for insertional mutagenesis poses a significant safety concern and barrier to wides...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.111
更新日期:2018-10-01 00:00:00
abstract::Trans-dominant mutants of human immunodeficiency virus type 1 (HIV-1) Tat and Rev are attractive candidates for use in gene therapy in the treatment of HIV-1 infections because both are essential for viral replication. Retroviral vectors were constructed to allow either Tat-inducible or Tat- and Rev-inducible expressi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1993.4.5-625
更新日期:1993-10-01 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
abstract::We evaluated the efficiency of gene transduction and of gene expression by adenoviral vectors in human lung adenocarcinoma cells. Freshly isolated cancer cells were collected from pleural effusions in adenocarcinoma patients by centrifugation with a Percoll gradient. Adenoviral vectors resulted in effective gene trans...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.1-1
更新日期:1997-01-01 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
pub_type: 杂志文章
doi:10.1089/hum.1997.8.17-2125
更新日期:1997-11-20 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::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::Glioblastomas account for approximately 20% of all primary brain tumors in adults. Glioblastoma multiforme (GBM) is a highly malignant tumor. In spite of advances in surgery, chemotherapy, and radiotherapy, the life expectancy of the patient with glioblastoma is approximately 11 months. To enhance glioma-specific gene...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/1043034041648372
更新日期:2004-08-01 00:00:00
abstract::Despite improvements in drug and device therapy for heart failure, hospitalization rates and mortality have changed little in the past decade. Randomized clinical trials using gene transfer to improve function of the failing heart are the focus of this review. Four randomized clinical trials of gene transfer in heart ...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2016.166
更新日期:2017-05-01 00:00:00
abstract::Deficiency of glycogen branching enzyme (GBE) causes glycogen storage disease type IV (GSD IV), which is characterized by the accumulation of a less branched, poorly soluble form of glycogen called polyglucosan (PG) in multiple tissues. This study evaluates the efficacy of gene therapy with an adeno-associated viral (...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2016.099
更新日期:2017-03-01 00:00:00
abstract::Adenoviral vectors used in gene therapy are predominantly derived from adenovirus serotype 5 (Ad5), which infects a broad range of cells. Ad5 cell entry involves interactions with the coxsackie-adenovirus receptor (CAR) and integrins. To assess these receptors in vivo, we mutated amino acid residues in fiber and pento...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303403765255165
更新日期:2003-05-20 00:00:00
abstract::The first report of in vivo gene delivery to the retina dates back to 1987 when a retroviral vector was injected intraocularly in newborn mice. Later came the observation that retinal cells could be successfully transduced using adenoviral and then adeno-associated and lentiviral vectors. By 2000, it had become clear ...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2017.164
更新日期:2017-11-01 00:00:00
abstract::Recombinant adenoviruses have great potential as gene delivery systems because of their ability to infect a wide range of target cells. However, systemic delivery of viral vectors to tissues other than liver and spleen has been inefficient because of the rapid clearance of the circulating virus by the liver. In the pr...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050015806
更新日期:2000-03-01 00:00:00
abstract::Clinical applications of gene therapy require advances in gene delivery systems. Although numerous clinical trials are already underway, the ultimate success of gene therapies will depend on gene transfer vectors that facilitate the expression of a specific gene at therapeutic levels in the desired cell populations wi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340360535751
更新日期:2003-02-10 00:00:00
abstract::Williams-Beuren syndrome (WBS) and supravalvular aortic stenosis (SVAS) are genetic syndromes marked by the propensity to develop severe vascular stenoses. Vascular lesions in both syndromes are caused by haploinsufficiency of the elastin gene. We used these distinct genetic syndromes as models to evaluate the feasibi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.201
更新日期:2012-11-01 00:00:00
abstract::We previously reported that spliceosome-mediated RNA trans-splicing (SMaRT), using recombinant adenoviral vectors expressing pre-trans-splicing molecules (PTMs), could partially restore cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity to polarized human DeltaF508 CF airway epithelia...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2005.16.1116
更新日期:2005-09-01 00:00:00
abstract::Expression of a gene encoding the diphtheria toxin A (DT-A) fragment, controlled by tissue specific regulatory elements, has previously been used to kill selected cell populations. Here, we have examined the feasibility of controlling DT-A expression using regulatory systems from the human immunodeficiency virus (HIV-...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1991.2.1-53
更新日期:1991-04-01 00:00:00
abstract::Human bocavirus type-1 (HBoV1) has a high tropism for the apical membrane of human airway epithelia. The packaging of a recombinant adeno-associated virus 2 (rAAV2) genome into HBoV1 capsid produces a chimeric vector (rAAV2/HBoV1) that also efficiently transduces human airway epithelia. As such, this vector is attract...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2017.060
更新日期:2017-08-01 00:00:00
abstract::At present, much more studies have focused on the role of microRNAs in osteoporosis, but the more specific role of microRNA-150-3p (miR-150-3p) in osteoporosis still needs full exploration. We aim at investigating the role of miR-150-3p in osteoporosis and at exploring the related mechanisms. Bone marrow mesenchymal s...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.005
更新日期:2021-01-22 00:00:00
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...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1089/104303401750298544
更新日期:2001-07-20 00:00:00
abstract::Adult T cell leukemia/lymphoma (ATL) is derived from CD4+ T cells and has a poor prognosis because of its resistance to chemotherapy. To evaluate the effectiveness of gene therapy for ATL, the effect of ganciclovir on ATL cell lines transfected with the thymidine kinase gene of herpes simplex virus type 1 (HSV-TK) was...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.18-2203
更新日期:1996-12-01 00:00:00
abstract::Human immunodeficiency virus (HIV) infection represents one of the most challenging systems for gene therapy. Thanks to the extended knowledge of the molecular biology of the HIV life cycle, many different strategies have been developed including transdominant modifications of HIV proteins, RNA decoys, antisense RNA, ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.5-621
更新日期:1998-03-20 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