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 previously shown that JAK3 gene transfer into irradiated recipients could restore immune function. However, since this toxic conditioning would be undesirable for infants in a clinical application, we have tested whether immune function could be restored in nonmyeloablated JAK3-deficient (-/-) mice. Murine JAK3 retroviral vectors were transduced into hematopoietic stem cells from the livers of newborn JAK3(-/-) mice. These cells were then injected intraperitoneally into nonirradiated JAK3(-/-) neonates. Transduced cells were detectable in these mice at time points 4 to 6 months after injection and resulted in significant correction of T and B lymphocyte numbers and circulating immunoglobulin (Ig) levels. After immune challenge with a dose of influenza A virus that was lethal to nonmanipulated JAK3(-/-) mice, mice injected with transduced cells showed development of circulating virus-specific IgG and enhanced survival. This work shows that the large selective advantage for JAK3-corrected lymphoid cells may be sufficient to overcome the need for myeloablative conditioning in JAK3 gene therapy protocols.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Bunting KD,Lu T,Kelly PF,Sorrentino BPdoi
10.1089/104303400750038462keywords:
subject
Has Abstractpub_date
2000-11-20 00:00:00pages
2353-64issue
17eissn
1043-0342issn
1557-7422journal_volume
11pub_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 T cell co-stimulatory molecule B7-1 was transduced into a poorly immunogenic murine neuroblastoma cell line (Neuro-2a, N-2a) alone or in combination with MHC class II genes to test the ability of these genes to stimulate antitumor immunity. N-2a cells transduced with B7-1 exhibited reduced tumorigenicity, whereas ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.17-2059
更新日期:1996-11-10 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::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::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::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::We employed the hypophysectomized rats as an animal model to explore the feasibility of using genetically engineered fibroblast cells for growth hormone gene therapy. An internal ribosome entry site (IRES)-directed bicistronic retroviral vector, PSN, which contained a porcine growth hormone (pGH) cDNA at the first cis...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1995.6.7-917
更新日期:1995-07-01 00:00:00
abstract::We report a novel method for targeting adenovirus-mediated gene delivery. By irradiating mammalian cells prior to adenoviral transduction, adenoviral gene transfer is greatly improved and the adenoviral genome integrates into cellular DNA. In this work, human and rodent cell lines were irradiated and subsequently tran...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.9-1025
更新日期:1997-06-10 00:00:00
abstract::Previous studies have documented that the skin can be used as a bioreactor to produce proteins for systemic release to treat diseases. A gene-switch system has been developed that allows regulated expression of therapeutic genes. To determine whether this system could be used in the skin, we developed a transgenic mou...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303402753812476
更新日期:2002-06-10 00:00:00
abstract::The practical application of gene transfer as a treatment for genetic diseases such as cystic fibrosis or hemophilia has been hindered, in part, by low efficiencies of vector delivery and transgene expression. We demonstrated that a feline immunodeficiency virus (FIV)-based lentiviral vector pseudotyped with the envel...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.127
更新日期:2007-12-01 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::Adoptive cellular therapy provides the promise of a potentially powerful general treatment for cancer. Although this is a complex and challenging field, there have been major advances in basic and translational research resulting in clinical trial activity that is now beginning to confirm this promise. However, these ...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2010.086
更新日期:2010-06-01 00:00:00
abstract::Ornithine transcarbamylase deficiency (OTCD) is an inborn error of urea synthesis that has been considered as a model for liver-directed gene therapy. Current treatment has failed to avert a high mortality or morbidity from hyperammonemic coma. Restoration of enzyme activity in the liver should suffice to normalize me...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340152712719
更新日期:2002-01-01 00:00:00
abstract::CTL lines directed against HIV-1 antigens were generated from infected individuals and were transduced by the HMB-K(b)HuIFNbeta vector, resulting in low, constitutive expression of interferon beta (IFN-beta). The IFN-beta-transduced cells showed markedly increased HIV-1-specific, MHC class I-restricted CTL activity ag...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950017482
更新日期:1999-07-20 00:00:00
abstract::Guidelines for testing gene therapy products for ecotropic replication-competent retrovirus (Eco-RCR) have not been delineated as they have for amphotropic viruses. To evaluate biologic assays that can detect these viruses, we compared an S(+)/L(-) assay and a marker rescue assay designed specifically for Eco-RCR dete...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303402760293619
更新日期:2002-09-20 00:00:00
abstract::Fibroblast-like synoviocytes (FLSs) participate in the pathogenesis of rheumatoid arthritis (RA). Emerging evidence has highlighted the role of long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and its potential involvement in RA. In this study, we test the hypothesis that the MALAT1 ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.212
更新日期:2019-08-01 00:00:00
abstract::Naked plasmid DNA electrotransfer offers advantages over viral-based gene delivery, including being regulatory permissive, but factors influencing expression efficiency and cell fate impact on translational utility. This study compared co-expression of red and green fluorescence reporter plasmids with differing promot...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.062
更新日期:2019-02-01 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::Immunologically sensitized recipients present one of the most critical problems in clinical organ transplantation today, since preformed antibodies rapidly destroy donor tissue expressing specific MHC class I antigens (Ag). Therefore, sensitized patients are either unable to receive a compatible organ, or experience a...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050015923
更新日期:2000-02-10 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::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::Duchenne muscular dystrophy (DMD) is a lethal genetic disorder for which there is currently no effective treatment. Although clinical application of adenoviral vector-mediated gene transfer has not been fully developed, it shows promise for the treatment of DMD. One significant problem posed by adenoviral vector-media...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1995.6.11-1477
更新日期:1995-11-01 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::For the successful application of RNA interference in vivo, it is desired to achieve (local) delivery of small interfering RNAs (siRNAs) and long-term gene silencing. Nonviral electrodelivery is suitable to obtain local and prolonged expression of transgenes. By intramuscular electrodelivery of a plasmid in which two ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.176
更新日期:2007-09-01 00:00:00
abstract::Pulmonary edema is cleared via active Na(+) transport by alveolar epithelial Na(+)/K(+)-ATPases and Na(+) channels. Rats exposed to acute hyperoxia have a high mortality rate, decreased Na(+)/K(+)-ATPase function, and decreased alveolar fluid clearance (AFC). We hypothesized that Na(+)/K(+)-ATPase subunit gene overexp...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303400750035753
更新日期:2000-11-01 00:00:00
abstract::Gene therapy for Duchenne muscular dystrophy will likely require that the corrective dystrophin gene be delivered to a high fraction of muscle fibers in vivo. Because of the large size of the dystrophin cDNA, adenoviral (Ad) vectors have been developed for this application. However, Ad vectors transduce mature muscle ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.314
更新日期:2006-03-01 00:00:00
abstract::Duchenne muscular dystrophy (DMD) typically occurs as a result of truncating mutations in the DMD gene that result in a lack of expression of the dystrophin protein in muscle fibers. Various therapies under development are directed toward restoring dystrophin expression at the subsarcolemmal membrane, including gene t...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2013.092
更新日期:2013-09-01 00:00:00
abstract::Esophageal cancer is characterized by rapid clinical progression and poor prognosis, due to early-stage invasion of adjacent tissues and metastasis. Tissue factor pathway inhibitor-2 (TFPI-2) has been implicated as a metastasis-associated gene in many types of tumors. Here we describe the potential involvement of TFPI...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2008.129
更新日期:2009-01-01 00:00:00
abstract::Eleven patients with moderate to severe erectile dysfunction (ED) were given a single-dose corpus cavernosum injection of hMaxi-K, a "naked" DNA plasmid carrying the human cDNA encoding hSlo (for human slow-poke), the gene for the alpha, or pore-forming, subunit of the human smooth muscle Maxi-K channel. Three patient...
journal_title:Human gene therapy
pub_type: 杂志文章,多中心研究
doi:10.1089/hum.2006.17.1165
更新日期:2006-12-01 00:00:00
abstract::Kallistatin is a serine proteinase inhibitor that has been shown to reduce joint swelling and to inhibit inflammation in a rat model of arthritis. In this study, we investigated the effect and mechanisms of kallistatin on cardiac function after myocardial ischemia-reperfusion (I/R) injury. The human kallistatin gene i...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.1201
更新日期:2006-12-01 00:00:00