Abstract:
:There is currently an urgent need to develop efficient gene-delivery systems for the lung that are free of inflammatory effects. The LID vector is a synthetic gene delivery system, comprised of lipofectin (L), an integrin-targeting peptide (I) and DNA (D) that has previously been shown to have high transfection efficiency in the lung. We have assessed the effect of alternative methods of complex preparation on structural features of the complex, levels and duration of reporter gene expression and the host response to the LID vector. We have demonstrated that making the complex in water affects the structure of the LID complexes making them smaller and more stable with a more cationic surface charge than complexes prepared in phosphate-buffered saline (PBS). When the LID vector was constituted in water and instilled intratracheally into the lungs of mice there was a 10-fold increase in luciferase activity compared with preparation in PBS. Furthermore, luciferase activity was still evident 1 week following vector instillation. This enhancement may be because of altered complex structure, although effects of the hypotonic vector solution on the lung cannot be excluded. The inflammatory effects of instilling the LID vector in water were minimal, even after three administrations of the LID vector, with only mild alterations in cytokine and broncho-alveolar lavage fluid (BALF) cell profiles. These results demonstrate that the LID vector can generate high, and prolonged, levels of gene expression in the lung from small quantities of DNA and that careful attention to synthetic polyplex structure may be important to optimize efficiency of gene expression in vivo.
journal_name
Gene Therjournal_title
Gene therapyauthors
Jenkins RG,Meng QH,Hodges RJ,Lee LK,Bottoms SE,Laurent GJ,Willis D,Ayazi Shamlou P,McAnulty RJ,Hart SLdoi
10.1038/sj.gt.3301963keywords:
subject
Has Abstractpub_date
2003-06-01 00:00:00pages
1026-34issue
12eissn
0969-7128issn
1476-5462pii
3301963journal_volume
10pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract::We introduce an injectable system for the formation of a biodegradable DNA-containing implant that releases DNA over a 2-month period to provide a robust and prolonged gene expression at the site. Sustained delivery of the appropriate plasmid DNA resulted in sustained expression of luciferase, the persistent appearanc...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301786
更新日期:2002-09-01 00:00:00
abstract::Replicating viruses for cancer gene therapy have beneficial antitumor effects, however, in the setting of an enzyme/prodrug system, the interactions between these viruses and the activated agents are complex. A replicating vaccinia virus expressing the cytosine deaminase gene (VVCD), which converts the prodrug 5-FC in...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301237
更新日期:2000-07-01 00:00:00
abstract::In order to characterize protein targeting signals in polarized postmitotic cortical neurones in vitro, we have developed recombinant and amplicon type vectors derived from herpes simplex virus 1 (HSV1) to transfer genes into these cells. We examined the targeting of both bacterial proteins, which lack specific target...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::The production of high-titer recombinant adeno-associated virus (rAAV) vector is essential for treatment of genetic diseases affecting the retina and choroid, where anatomical constraints may limit injectable volumes. Problematically, cytotoxicity arising from overexpression of the transgene during vector production f...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2017.50
更新日期:2017-08-01 00:00:00
abstract::Current generation adenovirus (Ad) vectors are deleted for the E1 region of genes and require propagation in E1 expressing 293 cells. Expression of genes delivered by Ad vectors into immunocompetent hosts is generally transient since the current vectors are not completely replication defective. Viral proteins expresse...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300378
更新日期:1997-03-01 00:00:00
abstract::We have used interleukin (IL)-4 and -10-producing HSV-1 gamma(1)34.5 deletion viruses in gene therapy of a BALB/c model of experimental allergic encephalomyelitis (EAE), a T cell-mediated demyelinating disease of the central nervous system. It is known that in EAE of mice the Th2-type cytokines are down-regulated and ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301465
更新日期:2001-05-01 00:00:00
abstract::A persistent obstacle in the use of vector systems for gene therapy has been the inability to attain high-level expression of the target gene in primary cells in vivo. The MFG retroviral vector was designed to yield improved expression over the widely used N2 or LN vectors; however, the molecular basis for this effect...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
abstract::Pancreatic cancer and chronic pancreatitis are clinical syndromes associated with severe pain that is difficult to manage. Thus, seeking additional pain reduction therapies is warranted. Excessive alcohol consumption over an extended period of time is the primary causal agent in pancreatitis. The efficacy of a replica...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/gt.2009.27
更新日期:2009-04-01 00:00:00
abstract::Angiogenesis plays a pivotal role in tumor growth, tissue invasion and metastasis. Endostatin is an angiogenesis inhibitor and has been shown to reduce tumor growth in animal models. However, therapy with recombinant endostatin protein was hampered by its short half-life and very-low yield of bioactive protein. We per...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3303038
更新日期:2008-02-01 00:00:00
abstract::Reactive oxygen species (ROS) have been implicated in the pathogenesis of rheumatoid arthritis (RA), while antioxidant enzymes, such as extracellular superoxide dismutase (EC-SOD) and catalase, block radical-induced events. The present study tested if the ex vivo transfer of EC-SOD and catalase genes alone or in combi...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301916
更新日期:2003-04-01 00:00:00
abstract::VP22, a structural protein from herpes simplex virus type I, exhibits the unique property of intercellular trafficking. This protein is exported from primary expressing cells and subsequently imported into neighbouring cells. This property is conserved when VP22 is genetically fused to a protein, making it a promising...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301904
更新日期:2003-02-01 00:00:00
abstract::Current experimental gene therapy approaches for Parkinson's disease (PD) and dementia with Lewy bodies (DLB) include the use of viral vectors expressing antiapoptosis genes, neurotrophic factors and dopaminergic system enzymes. However, since increasing evidence favors a role for alpha-synuclein accumulation in the p...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302349
更新日期:2004-12-01 00:00:00
abstract::Lentivirus can be engineered to be a highly potent vector for gene therapy applications. However, generation of clinical grade vectors in enough quantities for therapeutic use is still troublesome and limits the preclinical and clinical experiments. As a first step to solve this unmet need we recently introduced a bac...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.162
更新日期:2011-06-01 00:00:00
abstract::With the identification of stem cell plasticity several years ago, multiple reports raised hopes that tissue repair by stem cell transplantation could be within reach in the near future. Krause et al reported that a single purified hematopoietic stem cell not only repopulated the bone marrow of a host animal, but also...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302571
更新日期:2005-08-01 00:00:00
abstract::We have designed new vectors for the construction of recombinant adenoviruses containing expression cassettes in the E1 and/or E3 regions. Using a versatile set of restriction enzymes, the cassettes are cloned into small bacterial vectors and subsequently introduced into large plasmids containing the adenoviral sequen...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301047
更新日期:2000-01-01 00:00:00
abstract::Advances in genetic analysis and a greater understanding of human immunodeficiency virus (HIV) molecular pathogenesis have identified critical viral targets for gene interference strategies. RNase P molecules have been proposed as a novel approach for gene targeting based upon their potent catalytic activity, as well ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301606
更新日期:2001-12-01 00:00:00
abstract::Therapeutic RNA interference (RNAi) has emerged as a promising approach for the treatment of many incurable diseases, including cancer, infectious disease or neurodegenerative disorders. Demonstration of efficacy and safety in animal models is necessary before planning human application. Our group and others have prev...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2011.10
更新日期:2011-07-01 00:00:00
abstract::For certain gene therapy applications, the simultaneous delivery of multiple genes would allow for novel therapies. In the case of adeno-associated virus (AAV) vectors, the limited packaging capacity greatly restricts current methods of carrying multiple transgene cassettes. To address this issue, a recombinant AAV (r...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.106
更新日期:2009-11-01 00:00:00
abstract::The oncotropic phenotypes of several viruses correlate with tumor-associated deficiencies within interferon (IFN) signaling pathways. This observation formed the conceptual basis for developing oncolytic viruses deleted for viral proteins that inhibit the host IFN-dependent antiviral response, such as herpes simplex v...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.68
更新日期:2009-09-01 00:00:00
abstract::A novel class of cationic hyperbranched polymers, containing branched oligoethylenimine (OEI 800 Da) as core, diacrylate esters as linkers and oligoamines as surface modification, was synthesized and evaluated regarding their structure-activity relationship as gene carriers. We show that pseudodendritic core character...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3303046
更新日期:2008-01-01 00:00:00
abstract::Recombinant Autographa californica multiple nuclear polyhedrosis viruses (AcMNPV) have recently been shown to transduce mammalian cells in vitro. Since baculoviruses offer many advantages over viruses currently used in gene therapy, we have tested them for in vivo gene transfer by constructing a baculovirus bearing a ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301269
更新日期:2000-09-01 00:00:00
abstract::The potential of gene therapy for treatment of lung disease remains unrealised. Early model systems often resulted in promising efficiency of gene transfer, only to prove irreproducible in the clinic. While problems such as induction of host immune responses and duration of expression also need to be addressed, it is ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301146
更新日期:2000-04-01 00:00:00
abstract::Cultured keratinocyte allografts from unrelated donors can be readily grown as sheets in large-scale cell culture and have been used as an immediate skin cover for severely burned patients. Despite the absence of passenger leukocytes and the unlimited amount of material that can be obtained for permanent skin coverage...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301656
更新日期:2002-03-01 00:00:00
abstract::We have constructed two recombinant adeno-associated virus (AAV) vectors (pJJ-3GC and pJJ-3ASA) which contained either the human glucocerebrosidase (GC) or arylsulfatase A (ASA) cDNA under the control of an SV40 promoter. These plasmids were co-transfected to 293 cells with a helper plasmid containing trans-acting AAV...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::Gene therapy is thought to be a promising method for the treatment of various diseases. One gene therapy strategy involves the manipulations on a process of formation of new vessels, commonly defined as angiogenesis. Angiogenic and antiangiogenic gene therapy is a new therapeutic approach to the treatment of cardiovas...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302621
更新日期:2005-10-01 00:00:00
abstract::Viral therapy of cancer includes strategies such as viral transduction of tumour cells with 'suicide genes', using viral infection to trigger immune-mediated tumour cell death and using oncolytic viruses for their direct anti-tumour action. However, problems still remain in terms of adequate viral delivery to tumours....
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/gt.2010.48
更新日期:2010-08-01 00:00:00
abstract::There is growing interest in gene delivery to the eye in order to develop gene therapy for the many ocular disorders which may be amenable to this approach. To date, recombinant adenoviruses (AV) have been the main vector used for gene delivery to anterior and posterior segments in animal models. As with delivery to o...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300761
更新日期:1998-11-01 00:00:00
abstract::Growth factor therapy is an emerging treatment modality that enhances tissue vascularization, promotes healing and regeneration and can treat a variety of inflammatory diseases. Both recombinant human growth factor proteins and their gene therapy are in human clinical trials to heal chronic wounds. As platelet-derived...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.60
更新日期:2009-09-01 00:00:00
abstract::Intracerebral administration of recombinant adeno-associated vector (AAV) has been performed in several clinical trials. However, delivery into the brain requires multiple injections and is not efficient to target the spinal cord, thus limiting its applications. To assess widespread and less invasive strategies, we te...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2014.121
更新日期:2015-04-01 00:00:00
abstract::Hydrodynamic gene delivery is an attractive option for non-viral liver gene therapy, but requires evaluation of efficacy, safety and clinically applicable techniques in large animal models. We have evaluated retrograde delivery of DNA to the whole liver via the isolated segment of inferior vena cava (IVC) draining the...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3303079
更新日期:2008-03-01 00:00:00