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 transduced with the adenovirus vector Ad5CMVlacZ. Initial levels of transduction were as much as 40-fold higher in irradiated cells, and this improvement in transduction was radiation dose dependent. The duration of lacZ expression in irradiated cells was also much longer than in nonirradiated cells and reached a plateau after 21 days. At doses of 7 Gy, long-term (< 50 day) expression of lacZ could be detected in 15% of cells by flow cytometry. This long-lasting expression of lacZ was due to viral DNA integration into the host genome. Thus, pretreatment of cells with ionizing radiation improves both immediate transduction efficiency and duration of transgene expression. This may lead to the development of new protocols combining radiation and gene therapy in treating human malignancy.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Zeng M,Cerniglia GJ,Eck SL,Stevens CWdoi
10.1089/hum.1997.8.9-1025subject
Has Abstractpub_date
1997-06-10 00:00:00pages
1025-32issue
9eissn
1043-0342issn
1557-7422journal_volume
8pub_type
杂志文章abstract::Unlike oncoretroviruses, lentiviral vectors can insert large genes and can target both dividing and nondividing cells; thus they hold unique promise as gene transfer agents. To enhance target range, the native lentiviral envelope glycoprotein is replaced (pseudotyped) with vesicular stomatitis virus G (VSVG), and the ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340360464723
更新日期:2003-01-01 00:00:00
abstract::Vectors derived from the human parvovirus AAV-2 (adeno-associated virus type 2) are among the most promising gene delivery vehicles currently being developed. These vectors are not only capable of transducing a large variety of human cell types in vitro and in vivo, but in immunocompetent animal models can establish l...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/10430349950016799
更新日期:1999-10-10 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::Cell-based therapy for muscular dystrophies was initiated in humans after promising results obtained in murine models. Early trials failed to show substantial clinical benefit, sending researchers back to the bench, which led to the discovery of many hurdles as well as many new venues to optimize this therapeutic stra...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2015.139
更新日期:2016-02-01 00:00:00
abstract::Duchenne muscular dystrophy (DMD) and other inherited myopathies lead to progressive destruction of most skeletal muscles in the body, including those responsible for maintaining respiration. DMD is a fatal disorder caused by defects in the dystrophin gene. Recombinant adenovirus vectors (AdV) are considered a promisi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050015608
更新日期:2000-03-20 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::Therapeutic levels of expression of the beta-globin gene have been difficult to achieve with conventional retroviral vectors without the inclusion of DNase I-hypersensitive site (HS2, HS3, and HS4) enhancer elements. We generated recombinant adeno-associated viral (AAV) vectors carrying an antisickling human beta-glob...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2007.173
更新日期:2008-04-01 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::Oncolytic measles virus (MV) encoding the human thyroidal sodium iodide symporter (MV-NIS) has proved to be safe after intraperitoneal or intravenous administration in patients with ovarian cancer or multiple myeloma, respectively, but it has not yet been administered through intratumoral injection in humans. Squamous...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.128
更新日期:2012-03-01 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::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::Severe fetal growth restriction (FGR) affects 1:500 pregnancies, is untreatable and causes serious neonatal morbidity and death. Reduced uterine blood flow (UBF) and lack of bioavailable VEGF due to placental insufficiency is a major cause. Transduction of uterine arteries in normal or FGR sheep and guinea pigs using ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.006
更新日期:2020-11-01 00:00:00
abstract::Baculovirus vectors recently have been shown to be capable of efficient transduction of human hepatoma cells and primary hepatocytes in culture. This paper describes the generation of a novel recombinant baculovirus (VGZ3) in which the vesicular stomatitis virus glycoprotein G (VSV G) is present in the viral envelope....
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.17-2011
更新日期:1997-11-20 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::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::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 gro...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1993.4.4-433
更新日期:1993-08-01 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
abstract::Mucopolysaccharidosis type IIIA (MPSIIIA) is a rare lysosomal storage disorder caused by mutations in the sulfamidase gene. Accumulation of glycosaminoglycan (GAG) inside the lysosomes is associated with severe neurodegeneration as well as peripheral organ pathological changes leading to death of affected individuals ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2012.029
更新日期:2012-12-01 00:00:00
abstract::Targeted integration into a genomic safe harbor, such as the AAVS1 locus on chromosome 19, promises predictable transgene expression and reduces the risk of insertional mutagenesis in the host genome. The application of gamma-retroviral long terminal repeat (LTR)-driven vectors, which semirandomly integrate into the g...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2019.194
更新日期:2020-02-01 00:00:00
abstract::To achieve effective gene therapy, it is necessary to selectively and efficiently transfect therapeutic gene into targeted cells. In this study, we developed a combination method using mannosylated lipoplexes, which show selectivity to antigen-presenting cells such as macrophages and dendritic cells, and bubble liposo...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.106
更新日期:2010-01-01 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::Defined serum-free conditions have great conceptual advantages for the biological safety and standardization of clinical gene transfer into hematopoietic stem cells. In the only study reported to date, Sekhar et al. achieved low serum conditions by a complex concentration procedure of a retroviral supernatant initiall...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.6-771
更新日期:1998-04-10 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 influence of serum on the production of retroviral vectors by the HT1080 human fibrosarcoma-derived packaging cell line FLYRD18 was investigated. A fourfold increase in virus titer was observed under serum-free conditions, as compared with medium supplemented with 10% fetal calf serum. A similar improvement was al...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950017329
更新日期:1999-08-10 00:00:00
abstract::Recombinant poxviruses expressing immunomodulatory molecules together with specific antigens represent powerful vaccines for cancer immunotherapy. Recently, we and others have demonstrated, in vitro and in vivo, that coexpression of CD80 and CD86 costimulatory molecules enhances the immunogenic capacity of a recombina...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2005.16.348
更新日期:2005-03-01 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::Development of multidrug resistance (MDR) is the major obstacle to successful cancer chemotherapy. We have developed Daudi human lymphoma cells that are 20-fold more resistant than the parent cell line to vincristine (VCR) by infecting cells with pHaMDR1/A retroviral vector (Daudi/MDR20). Three DNA sequences of anti-M...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950018175
更新日期:1999-05-01 00:00:00
abstract::Malignant pleural mesothelioma (MPM) is a fatal disease with a median survival of less than 14 months. For the first time, a genetically engineered vaccinia virus is shown to produce efficient infection, replication, and oncolytic effect against MPM. GLV-1h68 is a replication-competent engineered vaccinia virus carryi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2008.036
更新日期:2008-08-01 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::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