Abstract:
:Recent marketing approval for genetically engineered hematopoietic stem and T cells bears witness to the substantial improvements in lentiviral vectors over the last two decades, but evaluations of the long-term efficacy and toxicity of gene and cell therapy products will, nevertheless, require further studies in nonhuman primate models. Macaca fascicularis monkeys from Mauritius have a low genetic diversity and are particularly useful for reproducible drug testing. In particular, they have a genetically homogeneous class I major histocompatibility complex system that probably mitigates the variability of the response to simian immunodeficiency virus infection. However, the transduction of simian cells with human immunodeficiency virus type 1 (HIV-1)-derived vectors is inefficient due to capsid-specific restriction factors, such as the tripartite motif-containing protein tripartite motif 5α, which prevent infection with non-host-adapted retroviruses. This study introduced the modified capsid of the macaque-trophic HIV-1 clone MN4/LSQD into the packaging system and compared transduction efficiencies between hematopoietic cells transduced with this construct and cells transduced with HIV-1 NL4-3-derived packaging constructs. Capsid modification increased transduction efficiency in all hematopoietic cells tested (by factors of up to 10), including hematopoietic progenitor cells, repopulating cells, and T cells from Mauritian Macaca fascicularis, regardless of vector structure or purification method. The study also established culture conditions similar to those used in clinical practice for the efficient transduction of hematopoietic stem and progenitor CD34+ cells. These results suggest that the procedure is suitable for use in Mauritian Macaca fascicularis, which can therefore be used as a model in preclinical studies for hematopoietic gene and cell therapy.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Sii-Felice K,Castillo Padilla J,Relouzat F,Cheuzeville J,Tantawet S,Maouche L,Le Grand R,Leboulch P,Payen Edoi
10.1089/hum.2018.179subject
Has Abstractpub_date
2019-10-01 00:00:00pages
1306-1323issue
10eissn
1043-0342issn
1557-7422journal_volume
30pub_type
杂志文章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::Silencing of Wnt antagonists with aberrant activation of Wnt signaling is a common phenomenon in various human cancers. Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist of Wnt signaling and acts through direct binding to Wnt in the extracellular space. In this study, we tried to illuminate the impact of WIF-1 ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.005
更新日期:2007-04-01 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::The management of disorders of the nervous system remains a medical challenge. The key goals are to understand disease mechanisms, to validate therapeutic targets, and to develop new therapeutic strategies. Viral vector-mediated gene transfer can meet these goals and vectors based on lentiviruses have particularly use...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2006.17.1
更新日期:2006-01-01 00:00:00
abstract::MDA-MB-231, an HLA-A2(+), HER2/neu(+) allogeneic breast cancer cell line genetically modified to express the costimulatory molecule CD80 (B7-1), was used to vaccinate 30 women with previously treated stage IV breast cancer. Expression of CD80 conferred the ability to deliver a costimulatory signal and thereby improved...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章
doi:10.1089/104303403322124828
更新日期:2003-07-20 00:00:00
abstract::The epithelial-mesenchymal transition (EMT) has been recognized to occur during embryonic development, fibrosis, and tumor metastasis. Nuclear factor (NF)-κB plays a central role in mediating the inflammation and wound-healing responses during liver fibrogenesis. However, the involvement of NF-κB during EMT in liver c...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2013.106
更新日期:2014-08-01 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::Traditionally, skeletal muscle and liver are the preferred target organs for gene transfer to supply a transgene product into the systemic circulation. In this respect, adipose tissue presents a number of attractive features. However, adipose tissue transduction in vivo has not been feasible by conventional methods. T...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.921
更新日期:2006-09-01 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::Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene that result in the absence of functional protein. In the majority of cases these are out-of-frame deletions that disrupt the reading frame. Several attempts have been made to restore the dystrophin mRNA reading frame by modulation of pre-m...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.061
更新日期:2007-09-01 00:00:00
abstract::Chronic inflammation in tibialis anterior muscles of mdx mice was produced by a single injection of a recombinant adenovirus vector (AV) expressing an immunogenic beta-galactosidase (beta-gal). In regions of intense beta-gal staining, mononuclear infiltrates abounded, and muscle fibers showed strong extrasynaptic utro...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2005.16.489
更新日期:2005-04-01 00:00:00
abstract::This multicenter phase I/II study evaluated the safety, pharmacokinetics, and antitumor effects of repeated doses of NV1020, a genetically engineered oncolytic herpes simplex virus, in patients with advanced metastatic colorectal cancer (mCRC). Patients with liver-dominant mCRC received four fixed NV1020 doses via wee...
journal_title:Human gene therapy
pub_type: 杂志文章,多中心研究
doi:10.1089/hum.2010.020
更新日期:2010-09-01 00:00:00
abstract::The combination of immunization strategies with gene therapy methods constitutes a powerful tool for the purpose of genetic immunization. The cutaneous microenvironment, rich in professional antigen-presenting cells and accessory cells capable of initiating and controlling the intensity of specific immune responses, m...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/104303400750035852
更新日期:2000-11-01 00:00:00
abstract::The potential of short interfering RNA (siRNA) to be developed for therapeutic use against cancer depends on the availability of an efficient tumor-specific delivery vehicle. We have previously shown that a nanoscale nonviral liposome-based complex that includes an anti-transferrin receptor single-chain antibody fragm...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.117
更新日期:2006-01-01 00:00:00
abstract::Gene-modified lymphocytes have a potential role in the therapy of cancer, infectious diseases, and genetic disorders of the immune system. Current gene therapy protocols involving gene transfer into lymphocytes utilize retroviruses with amphotropic envelope proteins. However, transduction efficiencies in lymphocytes u...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.12-1415
更新日期:1996-08-01 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::Adoptive cellular therapy has evolved into a powerful force in the battle against cancer, holding promise for curative responses in patients with advanced and refractory tumors. Autologous T cells, reprogrammed to target malignant cells via the expression of a chimeric antigen receptor (CAR) represent the frontrunner ...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2017.236
更新日期:2018-05-01 00:00:00
abstract::In vitro delivery of interferon-alpha (IFN-alpha) to cultured human monocytes by means of a replication-incompetent herpesvirus vector inhibits human immunodeficiency virus (HIV) replication. To explore the possibility of IFN-alpha gene delivery by vector-infected human monocytes, monocytes were isolated and the cultu...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.11-1331
更新日期:1996-07-10 00:00:00
abstract::Systemic administration of adenoviral vectors leads to activation of innate and antigen-specific immunity. In an attempt to diminish T and B cell-specific immune responses to E1-deleted adenoviral vectors, capsid proteins were modified with various activated monomethoxypolyethylene glycols (MPEGs). The impact of this ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303402760372972
更新日期:2002-10-10 00:00:00
abstract::Neurodegeneration in Parkinson's disease (PD) affects mainly dopaminergic neurons in the substantia nigra, where age-related, increasing percentages of cells lose detectable respiratory activity associated with depletion of intact mitochondrial DNA (mtDNA). Replenishment of mtDNA might improve neuronal bioenergetic fu...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.023
更新日期:2009-08-01 00:00:00
abstract::Recombinant adeno-associated virus 2 (rAAV2) has been extensively used as a gene delivery vector for the nervous system. It targets primarily neurons in the nervous system and results in sustained long-term expression of transgenes. New rAAV serotypes have been characterized and demonstrated to have improved transduct...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2005.16.781
更新日期:2005-07-01 00:00:00
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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::Janus kinase 3 (JAK3) is an essential component of cytokine receptor signal transduction pathways required for normal lymphocyte development and function. JAK3 deficiency in both mice and humans results in severe combined immunodeficiency (SCID) and increased susceptibility to opportunistic infections. We have previou...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303400750038462
更新日期:2000-11-20 00:00:00
abstract::Current clinical gene therapy protocols for the treatment of human immunodeficiency virus type 1 (HIV-1) infection often involve the ex vivo transduction and expansion of CD4+ T cells derived from HIV-positive patients at a late stage in their disease (CD4 count <400). These protocols involve the transduction of T cel...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.4-487
更新日期:1998-03-01 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::Restoration of correct splicing of βIVS2-654-globin pre-mRNA was previously accomplished in erythroid cells from β-thalassemia/HbE patients by an engineered U7 small nuclear RNA (snRNA) that carried a sequence targeted to the cryptic branch point and an exonic splicing enhancer, U7.BP+623 snRNA. In this study, this ap...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.145
更新日期:2020-11-02 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::Extracellular vesicles (EVs) being released from two adjacent adeno-associated virus serotype 1 (AAV1)-producing 293T cells are shown by electron microscopy. We have shown that AAV vectors can associate with EVs and enter the media. Furthermore, we have recently reported that EV-associated AAV has robust gene delivery...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2014.082
更新日期:2014-09-01 00:00:00
abstract::We evaluated the ability of a replication-deficient, recombinant adenoviral vector to transfer the bifunctional gene GAL-TEK, which expresses a marking/therapeutic gene product, to naturally occurring cat fibrosarcomas in situ. GAL-TEK contains an in-frame fusion of the bacterial LacZ gene for histochemical marking of...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1995.6.9-1215
更新日期:1995-09-01 00:00:00
abstract::T lymphocytes, regardless of their specificity, are considered key targets for genetic modification in the treatment of inherited or acquired human diseases. In this study, we generated Lewis T cell lines specific for Dark Agouti rat alloantigens and tested the potential of allospecific T lymphocytes as carriers of ge...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050032401
更新日期:2000-06-10 00:00:00