Abstract:
:Three retroviral constructs containing a full-length human alpha-L-iduronidase (IDUA) cDNA were made. The first, pLIdSN, is designed so that expression of the IDUA cDNA is from the 5' viral long terminal repeat (LTR). The second, pLNCId, is designed to express the IDUA cDNA from the cytomegalovirus (CMV) immediate early promoter, while in the third, pLNTId, the CMV promoter is replaced by a promoter fragment of the mouse CD45 (T200) gene. All vectors transduce resistance to G418 (neomycin). High-titer virus-producing cell lines for these constructs were made by infection of the amphotropic packaging cell line PA317 after transient expression in, and virus rescue from, the ecotropic packaging cell line psi CRE. The high-titer virus-producing cell lines were assayed for absence of helper virus, synthesis of human IDUA, and for integrity of proviral structure. Suitable lines were used as a source of virus to infect two different mucopolysaccharidosis type I (MPS I) skin fibroblast cultures. All three of the recombinant viruses corrected the enzymatic defect in MPS I fibroblasts. Surprisingly, increasing over-expression of IDUA resulted in reduced phenotypic correction of these cells as assayed by intracellular accumulation of 35S-labeled glycosaminoglycan. This was shown to be due to the induction of a phenotype analogous to mild I-cell disease in cells expressing large amounts of IDUA.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Anson DS,Bielicki J,Hopwood JJdoi
10.1089/hum.1992.3.4-371keywords:
subject
Has Abstractpub_date
1992-08-01 00:00:00pages
371-9issue
4eissn
1043-0342issn
1557-7422journal_volume
3pub_type
杂志文章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::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::The therapeutic use of neurotrophic factors for neurodegenerative diseases is promising, however, optimal methods for continuous delivery of these substances to the human central nervous system (CNS) remains problematic. One approach would be to graft genetically engineered human cells that continuously secrete high l...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.3-331
更新日期:1997-02-10 00:00:00
abstract::Classical gene therapy for cystic fibrosis has had limited success because of immune response against viral vectors and short-term expression of cDNA-based transgenes. These limitations could be overcome by delivering the complete genomic CFTR gene on nonintegrating human artificial chromosomes (HACs). Here, we report...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.225
更新日期:2010-09-01 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::Isolated methylmalonic acidemia (MMA), a group of autosomal recessive inborn errors of metabolism, is most commonly caused by complete (mut(0)) or partial (mut(-)) deficiency of the enzyme methylmalonyl-CoA mutase (MUT). The severe metabolic instability and increased mortality experienced by many affected individuals,...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2015.092
更新日期:2016-05-01 00:00:00
abstract::Due to both the avascularity of the cornea and the relatively immune-privileged status of the eye, corneal transplantation is one of the most successful clinical transplant procedures. However, in high-risk patients, which account for >20% of the 180,000 transplants carried out worldwide each year, the rejection rate ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2017.184
更新日期:2018-06-01 00:00:00
abstract::This study was designed to retrovirally transduce T cells by a protocol that would be simple, short, cost effective, applicable for clinical use, and efficient enough to avoid further selection of transduced T cells. Because retrovirally mediated infection is depending on the cell cycle, we first optimized the conditi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050015239
更新日期:2000-05-20 00:00:00
abstract::Systemic administration of currently manufactured viral stocks has not so far achieved sufficient circulating titers to allow therapeutic targeting of metastatic disease. This is due to low initial viral titers, immune inactivation, nonspecific adhesion, and loss of particles. One way to exploit the elegant molecular ...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/104303402760128504
更新日期:2002-07-20 00:00:00
abstract::Recombinant adeno-associated virus (AAV) holds much promise for human gene therapy. While evidence indicates that AAV mediates long-term gene transfer in several different tissues, difficulty in preparing and purifying this viral vector in large quantities remains a major obstacle for evaluating AAV vectors in clinica...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303400750001390
更新日期:2000-10-10 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::Gutted adenoviral (Ad) vectors have a greater cloning capacity and elicit less immune response than conventional Ad vectors. Unfortunately, clinical use of gutted vectors has been slowed by production difficulties, including low yield and a tendency for recombinant virus to emerge. These two problems are related, beca...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340252809810
更新日期:2002-03-01 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::Overexpression of human manganese-containing superoxide dismutase (MnSOD) activity has been demonstrated to suppress malignancy in human melanoma and breast carcinoma cells in vitro and in vivo. To study its effects on human oral squamous carcinoma cells, stable transfection and expression of MnSOD in SCC-25 cells hav...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.5-585
更新日期:1997-03-20 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::Adeno-associated virus (AAV) gene transfer is a promising treatment for genetic abnormalities. Optimal AAV vectors are showing success in clinical trials. Gene transfer to skeletal muscle and liver is being explored as a potential therapy for some conditions, that is, α1-antitrypsin (AAT) disorder and hemophilia B. Ex...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2016.073
更新日期:2016-11-01 00:00:00
abstract::Deoxyribozymes, or DNA enzymes (DNAzymes), are novel nucleic acids that have the ability to bind to specific sequences of RNA, and to cleave the target site catalytically. DNAzymes are smaller and more efficient enzymatically than ribozymes (RZs), which are catalytic nucleic acids synthesized from ribonucleotides. We ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950016573
更新日期:1999-11-20 00:00:00
abstract::This Phase I study, "Ribozyme Gene Therapy of HIV-1 Infection" (UCSD HSC #971072, FDA BB-IND 6405), is a prospective, open-label trial of infusion of autologous gene-altered cells into asymptomatic HIV-1 seropositive individuals. The objectives of this trial are to test the safety, feasibility, and potential efficacy ...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章
doi:10.1089/hum.1998.9.16-2407
更新日期:1998-11-01 00:00:00
abstract::Lentiviral vectors are efficient gene delivery vehicles for therapeutic and research applications. In contrast to oncoretroviral vectors, they are able to infect most nonproliferating cells. In the liver, induction of cell proliferation dramatically improved hepatocyte transduction using all types of retroviral vector...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.227
更新日期:2013-02-01 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::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::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::The utility of first-generation adenovirus vectors for long-term gene transfer in humans is limited by preexisting antiadenoviral immunity. We demonstrate here that new-generation high-capacity adenovirus vectors (HC-Ads) can efficiently transduce the brain and mediate stable transgene expression for at least 2 months...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401750148829
更新日期:2001-05-01 00:00:00
abstract::Based on the K8/JTS-1-mediated transfection technique, we developed an in vivo protocol for an efficient transfer of plasmid DNA to ocular cells. As determined with condensed plasmids containing reporter genes for either beta-galactosidase (pcDNA-lacZ) or enhanced green fluorescent protein (pREP-EGFP), the immortalize...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050129495
更新日期:2000-09-01 00:00:00
abstract::Successful gene transfer into articular cartilage is a prerequisite for gene therapy of articular joint disorders. In the present study we tested the hypothesis that recombinant adeno-associated virus (rAAV) vectors are capable of effecting gene transfer in isolated articular chondrocytes in vitro, articular cartilage...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303403321208998
更新日期:2003-03-01 00:00:00
abstract::Hematopoietic stem cells (HSCs) are a potential target for the retrovirus-mediated transfer of chemotherapeutic drug resistance genes. For integration of the proviral DNA in the HSC genome cell division is required. In the bone marrow (BM) hematopoiesis occurs in the vicinity of stroma cells. Soluble stroma components...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950017789
更新日期:1999-06-10 00:00:00
abstract::Establishing pharmacological parameters, such as efficacy, routes of administration, and toxicity, for recombinant adeno-associated virus (rAAV) vectors is a prerequisite for gaining acceptance for clinical applications. In fact, even a therapeutic window, that is, the dose range between therapeutic efficacy and toxic...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2009.092
更新日期:2009-08-01 00:00:00
abstract::Adenovirus-polylysine-DNA complexes were evaluated for their capacity to accomplish direct in vivo gene transfer to airway epithelium employing a rodent model. Binary complexes containing transferrin or adenovirus, or combination complexes containing both transferrin and adenovirus, were evaluated. The highest in vitr...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1993.4.1-17
更新日期:1993-02-01 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::Spinal muscular atrophy (SMA) is an autosomal recessive disease affecting ∼1 in 10,000 live births. The most striking component is the loss of α-motor neurons in the ventral horn of the spinal cord, resulting in progressive paralysis and eventually premature death. There is no current treatment paradigm other than sup...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2012.225
更新日期:2013-05-01 00:00:00