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 culture conditions necessary for efficient vector infection and gene expression were examined. Monocytes were efficiently infected between 1 and 7 days after isolation. Expression of IFN-alpha was greater in cells infected 7 days after isolation compared to 1 day after isolation, but the levels of expression were equivalent regardless of whether cells were maintained in suspension or monolayer culture. When suspension-cultured monocytes were treated with vd120/IFN-alpha and added to monolayer cultures of HIV-infected monocytes, IFN-alpha was expressed and replication of HIV was inhibited. HIV replication was arrested even when HIV had spread through much of the monolayer. The persistence of the viral vector in infected cells was examined by a superinfection rescue assay using a second replication-incompetent herpes simplex virus, 5dl1.2. The initial replication-incompetent vector remained in a recoverable form for at least 7 days after delivery, even though foreign gene expression was transient.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Weir JP,Dacquel EJ,Aronovitz Jdoi
10.1089/hum.1996.7.11-1331subject
Has Abstractpub_date
1996-07-10 00:00:00pages
1331-8issue
11eissn
1043-0342issn
1557-7422journal_volume
7pub_type
杂志文章abstract::Targeted vectors provide a number of advantages for systemic and local gene delivery strategies. Several groups have investigated the utility of using various ligands to alter the tropism of adenovirus (Ad) vectors. We have previously demonstrated that fibroblast growth factor (FGF) ligands can specifically target DNA...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050016265
更新日期:2000-01-01 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::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::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::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 nonh...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.179
更新日期:2019-10-01 00:00:00
abstract::Virotherapy is a unique modality for the treatment of cancer with oncolytic viruses (OVs) that selectively infect and lyse tumor cells, spread within tumors, and activate anti-tumor immunity. Various viruses are being developed as OVs preclinically and clinically, several of them engineered to encode therapeutic prote...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2017.138
更新日期:2017-10-01 00:00:00
abstract::Following in vivo recombinant adeno-associated virus (rAAV)-based gene transfer, adaptive immune responses specific to the vector or the transgene product have emerged as a potential roadblock to successful clinical translation. The occurrence of such responses depends on several parameters, including the route of vec...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2014.070
更新日期:2015-01-01 00:00:00
abstract::We report on an antitumor treatment involving electrogene therapy (EGT), a newly developed in vivo gene transfer method using electroporation. We carried out in vivo EGT in a subcutaneous model of CT26 colon carcinoma cells, using plasmid DNAs encoding interleukin 12 (IL-12) subunits. For this purpose, we developed tw...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401750270922
更新日期:2001-07-01 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::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::Introduction of a new vaccine requires choosing a delivery system that provides safe administration and the desired level of immunogenicity. The safety, tolerability, and immunogenicity of three monthly 2.5-mg doses of a PfCSP DNA vaccine were evaluated in healthy volunteers as administered intramuscularly (IM) by nee...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340260201644
更新日期:2002-09-01 00:00:00
abstract::Protein transduction domains (PTD), which can transport proteins or peptides across biological membranes, have been identified in several proteins of viral, invertebrate, and vertebrate origin. Here, we evaluate the immunological and biological consequences of including PTD in synthetic peptides and in DNA vaccines th...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401753153938
更新日期:2001-10-10 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::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::Nonviral jet injection is an applicable technology for in vivo gene transfer of naked DNA. However, little is known about the biodistribution and clearance of jet-injected DNA, or about its localization within tissue and cells. Therefore, in this study we analyzed the intratumoral and systemic biodistribution of jet-i...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.611
更新日期:2006-06-01 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::Oncolytic viruses (OV) are novel cancer gene therapies that are moving toward the forefront of modern medicines. However, their full therapeutic potential is hindered by the lack of convenient and reliable strategies to visualize and quantify OV growth kinetics and therapeutic efficacy in live cells. Here, we present ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.294
更新日期:2021-01-27 00:00:00
abstract::Human hematopoietic stem cells (HSCs) are poorly transduced by vectors based on adenovirus serotype 5 (Ad5). This is primarily due to the paucity of the coxsackievirus-Ad receptor on these cells. In an attempt to change the tropism of Ad5, we constructed a series of chimeric E1-deleted Ad5 vectors in which the shaft a...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401753204562
更新日期:2001-11-01 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::Despite efforts toward improvements in retrovirus-mediated gene transfer, stable high-level expression of a therapeutic gene in human hematopoietic stem cells remains a great challenge. We have evaluated the efficiency of different viral long terminal repeats (LTRs) in long-term expression of a transgene in vivo, usin...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401450942
更新日期:2001-01-01 00:00:00
abstract::The efficiency of gene therapy strategies against cancer is limited by the poor distribution of the vectors in the malignant tissues. To solve this problem, a new generation of tumor-specific, conditionally replicative adenoviruses is being developed. To direct the replication of the virus to breast cancer, we have co...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050143435
更新日期:2000-09-20 00:00:00
abstract::Hemophilia arthropathy (HA) represents the majority of morbidity in severe hemophilia patients, especially in resource-limited countries. Adeno-associated virus (AAV)-mediated gene therapy is showing promise for managing hemophilia. However, patients with neutralizing antibodies (NAbs) against AAV, and inhibitors to c...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2019.355
更新日期:2020-04-01 00:00:00
abstract::Airway infiltration by eosinophils is a major characteristic of chronic asthma. CCL11 (eotaxin-1) is secreted by lung epithelial cells and functions as the major chemokine for eosinophil recruitment. Pseudotyped adeno-associated virus (AAV) 2/9, composed by the AAV2 rep and AAV9 cap genes, can efficiently target lung ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2012.012
更新日期:2012-11-01 00:00:00
abstract::Adenovirus-based vectors comprise the most frequently used vector type in clinical studies to date. Both intense lab research and insights from the clinical trials reveal the importance of a comprehensive understanding of vector-host interactions. Especially for systemic intravenous adenovirus vector delivery, it is p...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2017.139
更新日期:2017-10-01 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::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::Antitumor gene therapy using herpes simplex type 1 thymidine kinase (TKh) and ganciclovir (GCV) treatment has revealed an important intratumoral bystander effect. A whole tumor can be eliminated when only a fraction of its tumor cells express TKh. We now report that the bystander effect not only acts within a tumor, b...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.15-1807
更新日期:1997-10-10 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::Peritoneal compartmentalization of advanced stage ovarian cancer provides a rational scenario for gene therapy strategies. Several groups are exploring intraperitoneal administration of adenoviral (Ad) vectors for this purpose. We examined in vitro gene transfer in the presence of ascites fluid from ovarian cancer pat...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050111313
更新日期:2000-08-10 00:00:00
abstract::To develop a potential gene therapy strategy for the treatment of hemophilia A, we constructed several retroviral vectors expressing a B-domain-deleted factor VIII (FVIII) cDNA. We confirmed previous reports that when the FVIII cDNA is inserted into a retroviral vector, the vector mRNA is decreased resulting in signif...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1995.6.11-1363
更新日期:1995-11-01 00:00:00