Abstract:
:If established cultured cell lines genetically modified to secrete desired gene products could be implanted in different allogeneic recipients without immune rejection, novel gene products would be delivered more cost effectively. We tested this strategy by encapsulating mouse Ltk- cells transfected with the human growth hormone (hGH) gene in immunoprotective perm-selective alginate microcapsules. Allogeneic mice implanted with these microcapsules demonstrated hGH in their circulation (0.1-1.5 ng/ml serum) within the first 2 weeks. Control mice implanted with only the transfected cells without microcapsules did not demonstrate significant levels of circulating hGH. By about 3 weeks, antibodies against hGH developed in the microcapsule-implanted mice. The immune response was detected only against the hGH and no other secretory products from the transfected cells. The antibody titer continued to escalate for more than three months, thus demonstrating indirectly the continued delivery of the growth hormone. The persistent expression of the transgene and survival of the transfected cells were verified when the microcapsules were retrieved periodically to demonstrate that the encapsulated cells remained viable, proliferative, and productive of hGH even by 78-111 days. In conclusion, delivering gene products with genetically modified allogeneic cells in vivo has been shown feasible for prolonged periods. This technology should have potential applications in somatic gene therapy and in treatment of other somatic diseases.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Chang PL,Shen N,Westcott AJdoi
10.1089/hum.1993.4.4-433subject
Has Abstractpub_date
1993-08-01 00:00:00pages
433-40issue
4eissn
1043-0342issn
1557-7422journal_volume
4pub_type
杂志文章abstract::Adeno-associated viral (AAV) vectors are becoming increasingly popular in basic research as well as in clinical gene therapy. Due to its exceptional resistance against physical and chemical stress, however, the increasing use of AAV in laboratories and clinics around the globe raises safety concerns. Proper decontamin...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.120
更新日期:2020-11-06 00:00:00
abstract::The optimal stem cell source for stem cell gene therapy has not been defined. Most gene transfer studies have used peripheral blood or marrow repopulating cells collected after administration of granulocyte colony-stimulating factor and stem cell factor (G-CSF/SCF). For clinical applications, however, growth factor ad...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303403322542329
更新日期:2003-11-20 00:00:00
abstract::The purpose of this study was to assess the therapeutic potential of injecting the gene for HLA-B7/beta2-microglobulin into the subcutaneous metastatic nodules of patients who are refractory to conventional treatments. The nine patients evaluated were divided into three groups and given escalating doses of DNA (20, 40...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.14-2031
更新日期:1998-09-20 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::The immune response against human immunodeficiency virus type-1 (HIV-1) is believed to play a role in controlling the early stages of disease progression. The cellular immune response, in particular cytotoxic T lymphocyte (CTL) activity, may be important for eliminating virally infected cells in HIV-1-infected individ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1994.5.7-853
更新日期:1994-07-01 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::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 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::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::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::Stem-cell therapy is a promising method for treating patients with a wide range of diseases and injuries. Increasing government funding of scientific research has promoted rapid developments in stem-cell research in China, as evidenced by the substantial increase in the number and quality of publications in the past 5...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2017.224
更新日期:2018-02-01 00:00:00
abstract::Somatic gene therapy for pulmonary diseases must be accomplished in vivo, requiring the spread of a gene transfer vector across a vast expanse of respiratory epithelium. Surfactant, a naturally occurring protein and lipid mixture used to treat the respiratory distress syndrome of prematurity, disperses rapidly and eve...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.2-171
更新日期:1997-01-20 00:00:00
abstract::In previous studies we showed that low-dose irradiation and immunosuppression with cyclosporine and mycophenolate mofetil prolonged in vivo persistence of gene-modified T cells but was unable to induce tolerance. We hypothesized that the lack of sustained antigen presentation because of the limited life span of the in...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2007.086
更新日期:2008-01-01 00:00:00
abstract::Here we show potent inhibition of HIV-1 replication in a human T cell line and primary human CD4(+) cells by expressing a single antiviral protein. Nullbasic is a mutant form of the HIV-1 Tat protein that was previously shown to strongly inhibit HIV-1 replication in nonhematopoietic cell lines by targeting three steps...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2012.176
更新日期:2013-03-01 00:00:00
abstract::We reported total correction of blood coagulation plasma factor VIII (FVIII) activity, using adeno-associated virus serotype 8 (AAV8) vectors for liver-specific gene transfer in hemophilia A mice. We now show, irrespective of immunosuppression or route of administration, total long-term correction of hemophilia A mice...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.427
更新日期:2006-04-01 00:00:00
abstract::CRISPR-based technology has been adapted to achieve a wide range of genome modifications including transcription regulation. The focus of this review is on the application of CRISPR-based platforms such as nuclease-deficient Cas9 and Cas12a, to achieve targeted gene activation. We review studies to date that have empl...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.241
更新日期:2021-01-15 00:00:00
abstract::At present there is no known effective pharmacological therapy for acute lung injury (ALI). Because keratinocyte growth factor (KGF) promotes epithelial cell growth, intratracheal administration of KGF has the possibility of restoring lung tissue integrity in injured lungs and improving patient outcomes. However, trea...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.137
更新日期:2007-02-01 00:00:00
abstract::Cell-based gene transfer using a stent platform would provide a significant advantage in terms of site-specific gene expression in the vasculature. The current study presents a novel stent design that allows stable in vivo transgene expression over a 4-week period in the vasculature. A mesh-stent coated with fibronect...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340252792567
更新日期:2002-02-10 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::Three dogs with deficiency of the lysosomal enzyme alpha-L-iduronidase were treated by gene replacement therapy targeted at muscle. Direct intramuscular injections of plasmid encoding the alpha-L-iduronidase gene cDNA resulted in no detectable enzyme production, but may have resulted in immunologic sensitization to id...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.13-1595
更新日期:1996-08-20 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::Subcutaneous vaccination therapy with glioma cells, which are retrovirally transduced to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF), has previously proven effective in C57BL/6 mice harboring intracerebral GL261 gliomas. However, clinical ex vivo gene therapy for human gliomas would be difficult,...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050057503
更新日期:2000-07-01 00:00:00
abstract::Production of clinical-grade gammaretroviral vectors for ex vivo gene delivery requires a scalable process that can rapidly generate large amounts of vector supernatant, clear large numbers of residual packaging cells with minimal decreases in vector titer, and satisfy all current regulatory guidelines regarding produ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2010.064
更新日期:2011-01-01 00:00:00
abstract::Evaluation of the potential role of dendritic cells (DCs) as adjuvants for tumor vaccination has focused primarily on techniques that load DCs with peptide tumor antigens. Our aim has been to optimize the induction of antitumor immunity by enhancing the ability of DCs to present tumor-associated antigens endogenously ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.11-1355
更新日期:1997-07-20 00:00:00
abstract::Interleukin (IL)-12 has been reported to induce cellular immune responses for protection against tumor formation. Here we investigate the utility of adenoviral delivery of IL-12 as an adjuvant for a human papillomavirus E7 subunit vaccine in a mouse tumor challenge model. Direct intratumoral injection of AdIL-12 resul...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303403769211619
更新日期:2003-10-10 00:00:00
abstract::Advances in cell and gene therapy are opening up new avenues for regenerative medicine. Because of their acquired pluripotency, human induced pluripotent stem cells (hiPSCs) are a promising source of autologous cells for regenerative medicine. They show unlimited self-renewal while retaining the ability, in principle,...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2012.251
更新日期:2013-06-01 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::Rat myoblast primary cultures were tested as a model for proinsulin synthesis and processing and unregulated insulin delivery for insulin-dependent diabetes mellitus (IDDM) gene therapy. Three human proinsulin cDNA constructs containing genetically engineered furin endoprotease cleavage sites between the B-chain and C...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.1-71
更新日期:1996-01-01 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::Replication-competent adenoviruses may provide a highly efficient means of delivering therapeutic genes to tumors. Previously, we evaluated in vitro a replication-competent adenovirus (Ad5-CD/TKrep) containing a cytosine deaminase (CD)/herpes simplex type 1 thymidine kinase (HSV-1 TK) fusion gene that allows lytic vir...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050016166
更新日期:2000-01-01 00:00:00