Abstract:
:Gene delivery via murine-based recombinant retroviral vectors is currently widely used in gene therapy clinical trials. The vectors are engineered to be replication defective by replacing the structural and nonstructural genes of a cloned infectious retrovirus with a therapeutic gene of interest. The retroviral particles are currently generated in packaging cell lines, which supply all retroviral proteins in trans. Recombination between short homologous regions of the retroviral vector and packaging cell line elements can theoretically generate replication-competent retrovirus (RCR) and hence the Food and Drug Administration (FDA) requires the monitoring of clinical trial subjects for the presence of RCR. Sensitive polymerase chain reaction (PCR) assays have been used for the detection of murine leukemia virus (MLV) nucleotide sequences in peripheral blood mononuclear cells (PBMCs). A novel serological enzyme-linked immunosorbent assay (ELISA) for the detection of anti-MLV specific immunoglobulin (Ig) has been developed to be used as an alternative to the PCR assay. Both assays were used to monitor human immunodeficiency virus (HIV)-positive clinical trial subjects who had received multiple injections of HIV-IT (V), a retroviral vector encoding HIV-1 IIIBenv/rev. Western blot analysis and an in vitro vector neutralization assay were used to characterize further a subset of serum samples tested by ELISA. Results show no evidence of RCR infection in clinical trial subjects. PCR and ELISA assays are discussed in terms of their advantages and limitations as routine screening assays for RCR. The PCR assay is our current choice for monitoring clinical trial subjects receiving direct administration of vector, and the ELISA is our choice for those receiving ex vivo treatment regimens.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Martineau D,Klump WM,McCormack JE,DePolo NJ,Kamantigue E,Petrowski M,Hanlon J,Jolly DJ,Mento SJ,Sajjadi Ndoi
10.1089/hum.1997.8.10-1231subject
Has Abstractpub_date
1997-07-01 00:00:00pages
1231-41issue
10eissn
1043-0342issn
1557-7422journal_volume
8pub_type
杂志文章abstract::Replication-deficient adenoviruses are known to induce acute injury and inflammation of infected tissues, thus limiting their use for human gene therapy. However, molecular mechanisms triggering this response have not been fully defined. To characterize this response, chemokine expression was evaluated in DBA/2 mice f...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950018364
更新日期:1999-04-10 00:00:00
abstract::Genome engineering has gone mainstream because of breakthroughs in defining and harnessing naturally occurring, customizable DNA recognition cursors (protein or RNA-guided). At present, most gene editing relies on these cursors to direct custom DNA endonucleases to a specific genomic sequence to induce a double-strand...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2016.071
更新日期:2016-06-01 00:00:00
abstract::Laminin-5 is composed of three distinct polypeptides, alpha3, beta3, and gamma2, which are encoded by three different genes, LAMA3, LAMB3, and LAMC2, respectively. We have isolated epidermal keratinocytes from a patient presenting with a lethal form of junctional epidermolysis bullosa characterized by a homozygous mut...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.9-1359
更新日期:1998-06-10 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::Adeno-associated viral vectors are showing great promise as gene therapy vectors for a wide range of retinal disorders. To date, evaluation of therapeutic approaches has depended almost exclusively on the use of animal models. With recent advances in human stem cell technology, stem cell-derived retina now offers the ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.027
更新日期:2018-10-01 00:00:00
abstract::Human immunodeficiency virus (HIV) infection represents one of the most challenging systems for gene therapy. Thanks to the extended knowledge of the molecular biology of the HIV life cycle, many different strategies have been developed including transdominant modifications of HIV proteins, RNA decoys, antisense RNA, ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.5-621
更新日期:1998-03-20 00:00:00
abstract::Immunoisolation of allogeneic cells within a membrane-bound device is a unique approach for gene therapy. We employed an immunoisolation device that protects allograft, but not xenograft, cells from destruction, to implant a human fibroblast line (MSU 1.2) in athymic rodents. Cells, transduced with the MFG-human facto...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.6-879
更新日期:1998-04-10 00:00:00
abstract::Engineered measles virus (MV) strains deriving from the vaccine lineage represent a promising oncolytic platform and are currently being tested in phase I trials. In this study, we have demonstrated that MV strains genetically engineered to express the human sodium iodide symporter (NIS) have significant antitumor act...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.158
更新日期:2012-04-01 00:00:00
abstract::Human papillomavirus type 16 (HPV16) is associated with the development of anogenital cancers and their precursor lesions, intraepithelial neoplasia. Treatment strategies against HPV-induced intraepithelial neoplasia are not HPV specific and mostly consist of physical removal or ablation of lesions. We had previously ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.115
更新日期:2010-07-01 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::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::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::Immunotherapy with whole cell cancer vaccines has been tested in various tumor types. This study investigated the safety profile and antitumor activity of an allogeneic prostate carcinoma cell line, LNCaP, expressing recombinant human interleukin-2 and human interferon-gamma. Thirty HLA-A*0201-matched patients with pr...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.101
更新日期:2009-12-01 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::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::The gene therapy strategy using the hsvl-thymidine kinase gene (TK) and ganciclovir (GCV) injections that has been used for treating human glioblastomas has not been as effective as expected after the first animal experiments. A better understanding of the different steps involved in this treatment, like gene transfer...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.16-1945
更新日期:1997-11-01 00:00:00
abstract::In previous studies we demonstrated that a modified human HSP70b promoter (HSE.70b) directs high levels of gene expression to tumor cells after mild hyperthermia treatment in the range of 41.5-44 degrees C. This transcriptional targeting system exhibits low basal activity at 37 degrees C, is highly induced (950-fold) ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303403321467216
更新日期:2003-03-20 00:00:00
abstract::Engineering gene therapy vectors to modulate the immune response is an important goal. In this regard, costimulation of T cells is a critical determinant in immune activation. The costimulatory molecule CD40, expressed on antigen-presenting cells, is thought to interact with CD40 ligand (CD40L) expressed on activated ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401750214302
更新日期:2001-06-10 00:00:00
abstract::Diabetes mellitus is associated with increased risk of heart failure. It has been previously demonstrated in mice that a single injection of adeno-associated virus 8 encoding urocortin 2 (AAV8.UCn2) increases glucose disposal in models of insulin resistance and improves the function of the failing heart. The present s...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.150
更新日期:2019-06-01 00:00:00
abstract::The ability to control proliferation of grafted cells in the heart and consequent graft size could dramatically improve the efficacy of cell therapies for cardiac repair. To achieve targeted graft cell proliferation, we created a chimeric receptor (F36Vfgfr-1) composed of a modified FK506-binding protein (F36V) fused ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.161
更新日期:2007-05-01 00:00:00
abstract::Abstract Our studies have shown that coinjection of conventional single-stranded adeno-associated virus 2 (ssAAV2) vectors carrying the enhanced green fluorescent protein (EGFP) gene with self-complementary (sc) AAV2-T cell protein tyrosine phosphatase (TC-PTP) and scAAV2-protein phosphatase-5 (PP5) vectors resulted i...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.100
更新日期:2010-03-01 00:00:00
abstract::Extension of in vivo nucleic acid transfection techniques and increased information about those transfection properties and side effects are urgently needed to advance biological research and drug therapy. Tissue pressure-mediated transfection, involving lightly pressing the target tissue after intravenous injection o...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2008.213
更新日期:2009-10-01 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::Recombinant vectors based on adeno-associated virus serotype 8 (AAV8) have been successfully used in the clinic and hold great promise for liver-directed gene therapy. Preexisting immunity against AAV8 or the development of antibodies against the therapeutic transgene product might negatively affect the outcomes of ge...
journal_title:Human gene therapy
pub_type: 杂志文章,多中心研究
doi:10.1089/hum.2014.109
更新日期:2015-03-01 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::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::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::In the next decades, gene editing technologies are expected to be used in the treatment and prevention of human diseases. Yet, the future uses of gene editing in medicine are still unknown, including its applicability and effectiveness to the treatment and prevention of infectious diseases, cancer, and monogenic and p...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.136
更新日期:2020-08-01 00:00:00
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::Abstract Malignant gliomas (MGs) are highly vascularized, aggressive brain cancers carrying a dismal prognosis. Because of their high vascularity, anti-angiogenic therapy is a potential treatment option. Indeed, the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has demonstrated promising results ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2013.191
更新日期:2014-11-01 00:00:00