Gene therapy in autoimmune, demyelinating disease of the central nervous system.

Abstract:

:Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS), where suspected autoimmune attack causes nerve demyelination and progressive neurodegeneration and should benefit from both anti-inflammatory and neuroprotective strategies. Although neuroprotection strategies are relatively unexplored in MS, systemic delivery of anti-inflammatory agents to people with MS has so far been relatively disappointing. This is most probably because of the limited capacity of these molecules to enter the target tissue, because of exclusion by the blood-brain barrier. The complex natural history of MS also means that any therapeutic agents will have to be administered long-term. Gene therapy offers the possibility of site-directed, long-term expression, and is currently being preclinically investigated in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. While some immune effects may be targeted in the periphery using DNA vaccination, strategies both viral and nonviral are being developed to target agents into the CNS either via direct delivery or using the trafficking properties of cell-carrier systems. Targeting of leucocyte activation, cytokines and nerve growth factors have shown some promising benefit in animal EAE systems, the challenge will be their application in clinical use.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Baker D,Hankey DJ

doi

10.1038/sj.gt.3302025

keywords:

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

844-53

issue

10

eissn

0969-7128

issn

1476-5462

pii

3302025

journal_volume

10

pub_type

杂志文章,评审
  • An antiaggregation gene therapy strategy for Lewy body disease utilizing beta-synuclein lentivirus in a transgenic model.

    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

    authors: Hashimoto M,Rockenstein E,Mante M,Crews L,Bar-On P,Gage FH,Marr R,Masliah E

    更新日期:2004-12-01 00:00:00

  • Human PBMC-derived dendritic cells transduced with an adenovirus vectorinduce cytotoxic T-lymphocyte responses against a vector-encoded antigen in vitro.

    abstract::Dendritic cells (DC) are among the most potent antigen-presenting cells known and play an important role in the initiation of antigen-specific T-lymphocyte responses. Several recent studies have demonstrated that DC expressing vector-encoded tumor-associated antigens can induce protective and therapeutic immunity in m...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300899

    authors: Diao J,Smythe JA,Smyth C,Rowe PB,Alexander IE

    更新日期:1999-05-01 00:00:00

  • Efficient adventitial gene delivery to rabbit carotid artery with cationic polymer-plasmid complexes.

    abstract::Different lipids and cationic polymers were tested in vitro for their ability to transfect rabbit aortic smooth muscle cells and human endothelial cells with lacZ marker gene. Toxicity of the complexes was evaluated with MTT assay. Selected plasmid-polymer complexes with different charge ratios were then tested for in...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300800

    authors: Turunen MP,Hiltunen MO,Ruponen M,Virkamäki L,Szoka FC Jr,Urtti A,Ylä-Herttuala S

    更新日期:1999-01-01 00:00:00

  • Enhanced in vivo adenovirus-mediated gene transfer to rat hepatocarcinomas by selective administration into the hepatic artery.

    abstract::Adenovirus-mediated gene therapy of experimental hepatocarcinoma is hindered by low transduction efficacy in vivo. We evaluated the extent of gene expression following various routes of administration of recombinant adenovirus AdCMVlacZ in diethylnitrosamine-induced rat hepatocarcinoma. We first characterized the vasc...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300664

    authors: Gérolami R,Cardoso J,Bralet MP,Cuenod CA,Clément O,Tran PL,Bréchot C

    更新日期:1998-07-01 00:00:00

  • Augmentation of myocardial transfection using TerplexDNA: a novel gene delivery system.

    abstract::Gene therapy is a potential new strategy for the treatment of cardiovascular disease. The most efficacious method of gene delivery remains a key hurdle to effective gene therapy. We present the application of a novel, nonviral gene delivery system (TerplexDNA) to augment myocardial transfection. The hearts of New Zeal...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301395

    authors: Affleck DG,Yu L,Bull DA,Bailey SH,Kim SW

    更新日期:2001-03-01 00:00:00

  • In vivo gene introduction into keratinocytes using jet injection.

    abstract::Successful keratinocyte gene therapy requires the development of efficient methods of gene transfer to keratinocytes. Jet injection of a solution containing DNA can be used to transfer genes to several tissues in vivo. In this article, we tried to introduce DNA into rat and human keratinocytes using this method. First...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301002

    authors: Sawamura D,Ina S,Itai K,Meng X,Kon A,Tamai K,Hanada K,Hashimoto I

    更新日期:1999-10-01 00:00:00

  • Bicistronic retroviral vectors for combining myeloprotection with cell-surface marking.

    abstract::We have developed a retroviral vector coexpressing the multidrug-resistance 1 (MDR1) cDNA for inducing cancer drug resistance and the truncated version of the low-affinity nerve growth factor receptor (DeltaLNGFR) for cell-surface marking of transduced cells. The vector is based on the FMEV backbone which mediates hig...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300942

    authors: Hildinger M,Schilz A,Eckert HG,Bohn W,Fehse B,Zander A,Ostertag W,Baum C

    更新日期:1999-07-01 00:00:00

  • Tetracycline-inducible transgene expression mediated by a single AAV vector.

    abstract::Regulated gene delivery systems are usually made of two elements: an inducible promoter and a transactivator. In order to optimize gene delivery and regulation, a single viral vector ensuring adequate stoichiometry of the two elements is required. However, efficient regulation is hampered by interferences between the ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301838

    authors: Chtarto A,Bender HU,Hanemann CO,Kemp T,Lehtonen E,Levivier M,Brotchi J,Velu T,Tenenbaum L

    更新日期:2003-01-01 00:00:00

  • Inhibition of NF-kappaB enhances the cytotoxicity of virus-directed enzyme prodrug therapy and oncolytic adenovirus cancer gene therapy.

    abstract::Virus-directed enzyme prodrug therapy utilizing the bacterial enzyme nitroreductase delivered by a replication-defective adenovirus vector to activate the prodrug CB1954 is a promising strategy currently undergoing clinical trials in patients with a range of cancers. Similarly, selectively replicating oncolytic adenov...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302510

    authors: Palmer DH,Chen MJ,Searle PF,Kerr DJ,Young LS

    更新日期:2005-08-01 00:00:00

  • Intracellular rate-limiting steps of gene transfer using glycosylated polylysines in cystic fibrosis airway epithelial cells.

    abstract::To identify the intracellular barriers to efficient gene transfer, we studied the intracellular trafficking of biotinylated plasmid DNA complexed with either fluorescein-conjugated lactosylated or mannosylated polylysine by confocal microscopy. Both are known to be taken up by cystic fibrosis airway epithelial cells (...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301768

    authors: Grosse S,Tremeau-Bravard A,Aron Y,Briand P,Fajac I

    更新日期:2002-08-01 00:00:00

  • Herpesvirus microRNAs for use in gene therapy immune-evasion strategies.

    abstract::Transplantation of allogeneic cells as well as of genetically corrected autologous cells are potent approaches to restore cellular functions in patients suffering from genetic diseases. The recipient's immune responses against non-self-antigens may compromise the survival of the grafted cells. Recipients of the graft ...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/gt.2017.37

    authors: Bots STF,Hoeben RC

    更新日期:2017-07-01 00:00:00

  • An optimum anti-melanoma response in mice immunized with fibroblasts transfected with DNA from mouse melanoma cells requires the expression of both syngeneic and allogeneic MHC-determinants.

    abstract::Most neoplasms do not induce antitumor immune responses that can control tumor growth. Tumor associated antigens (TAAs) are insufficiently immunogenic. A vaccine that augments the immunogenic properties of TAAs could be of importance in the treatment of cancer patients. In an animal model, we prepared a vaccine by tra...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301765

    authors: de Zoeten EF,Markovic D,Cohen EP

    更新日期:2002-09-01 00:00:00

  • Enhanced immune costimulatory activity of primary acute myeloid leukaemia blasts after retrovirus-mediated gene transfer of B7.1.

    abstract::Gene modification of malignant cells to express immune stimulators (cytokines and immune costimulators) has provided the basis for a novel form of immunotherapy. Using a MPSV-based retroviral vector with hygromycin resistance gene as a selectable marker, we have studied retrovirus-mediated gene transfer of an immune c...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300437

    authors: Hirst WJ,Buggins A,Darling D,Gäken J,Farzaneh F,Mufti GJ

    更新日期:1997-07-01 00:00:00

  • Use of transcriptional regulatory elements of the MUC1 and ERBB2 genes to drive tumour-selective expression of a prodrug activating enzyme.

    abstract::In order to exploit differences in gene expression between normal and malignant cells for genetic prodrug-activation therapy, we have generated recombinant retroviruses containing the herpes simplex virus thymidine kinase coding region cloned downstream of sequences derived from the 5'-flanking regions of the MUC1 and...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300510

    authors: Ring CJ,Blouin P,Martin LA,Hurst HC,Lemoine NR

    更新日期:1997-10-01 00:00:00

  • Vero/BC-F: an efficient packaging cell line stably expressing F protein to generate single round-infectious human parainfluenza virus type 2 vector.

    abstract::A stable packaging cell line (Vero/BC-F) constitutively expressing fusion (F) protein of the human parainfluenza virus type 2 (hPIV2) was established for production of the F-defective and single round-infectious hPIV2 vector in a strategy for recombinant vaccine development. The F gene expression has not evoked cytost...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2014.55

    authors: Ohtsuka J,Fukumura M,Tsurudome M,Hara K,Nishio M,Kawano M,Nosaka T

    更新日期:2014-08-01 00:00:00

  • Control of parvovirus DNA replication by a tetracycline-regulated repressor.

    abstract::Autonomous parvoviruses are small, single strand DNA viruses which preferentially replicate in transformed and tumor cells, causing cell death by expression of the cytotoxic nonstructural protein, NS1. Several parvoviruses of the rodent group, including LuIII, efficiently infect human transformed cell lines. The poten...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300832

    authors: Maxwell IH,Maxwell F

    更新日期:1999-03-01 00:00:00

  • GCV phosphates are transferred between HeLa cells despite lack of bystander cytotoxicity.

    abstract::The role of gap junctional intercellular communication (GJIC) in bystander killing with herpes simplex virus thymidine kinase (HSV-TK) and ganciclovir (GCV) was evaluated in U251 cells expressing a dominant-negative connexin 43 cDNA (DN14), and in HeLa cells, reportedly devoid of connexin protein. These cell lines bot...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302487

    authors: Gentry BG,Im M,Boucher PD,Ruch RJ,Shewach DS

    更新日期:2005-07-01 00:00:00

  • Imaging the spatial distribution of transgene expression in the lungs with positron emission tomography.

    abstract::This study was designed to evaluate the utility of positron emission tomography (PET) to quantify the magnitude and spatial distribution of transgene expression after different methods of adenoviral vector delivery (with surfactant- and saline-based vehicles) within rat lungs. In all, 17 animals (eight in the surfacta...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302117

    authors: Richard JC,Factor P,Welch LC,Schuster DP

    更新日期:2003-12-01 00:00:00

  • Potent antitumor activity of oncolytic adenovirus-mediated SOCS1 for hepatocellular carcinoma.

    abstract::Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in diverse cancers, which contributes to the proliferation and survival of cancer cells by upregulating apoptosis inhibitors and cell cycle regulators. Suppressor of cytokine signaling 1 (SOCS1) is an important negative regulator of...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2012.4

    authors: Liu L,Li W,Wei X,Cui Q,Lou W,Wang G,Hu X,Qian C

    更新日期:2013-01-01 00:00:00

  • Bidirectional promoter interference between two widely used internal heterologous promoters in a late-generation lentiviral construct.

    abstract::Gene transfer vectors encoding two or more genes are potentially powerful research tools and are poised to play an increasingly important role in gene therapy applications. Common strategies employed to express more than one transgene per vector include the use of multiple promoters, internal ribosome entry site (IRES...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3303105

    authors: Curtin JA,Dane AP,Swanson A,Alexander IE,Ginn SL

    更新日期:2008-03-01 00:00:00

  • Effect of decorin on overcoming the extracellular matrix barrier for oncolytic virotherapy.

    abstract::The pressing challenge for contemporary gene therapy is to deliver enough therapeutic genes to enough cancer cells in vivo. With the aim of improving viral distribution and tumor penetration, we explored the use of decorin to enhance viral spreading and tumor tissue penetration. We generated decorin-expressing replica...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2009.142

    authors: Choi IK,Lee YS,Yoo JY,Yoon AR,Kim H,Kim DS,Seidler DG,Kim JH,Yun CO

    更新日期:2010-02-01 00:00:00

  • VEGF-expressing human umbilical cord mesenchymal stem cells, an improved therapy strategy for Parkinson's disease.

    abstract::The umbilical cord provides a rich source of primitive mesenchymal stem cells (human umbilical cord mesenchymal stem cells (HUMSCs)), which have the potential for transplantation-based treatments of Parkinson's Disease (PD). Our pervious study indicated that adenovirus-associated virus-mediated intrastriatal delivery ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2010.152

    authors: Xiong N,Zhang Z,Huang J,Chen C,Zhang Z,Jia M,Xiong J,Liu X,Wang F,Cao X,Liang Z,Sun S,Lin Z,Wang T

    更新日期:2011-04-01 00:00:00

  • In vivo targeted gene transfer into liver cells mediated by a novel galactosyl-D-lysine/D-serine copolymer.

    abstract::A novel synthetic polypeptide designed as a DNA binding-molecule for liver-specific, receptor-mediated, gene transfer was used to selectively introduce reporter genes into liver cells in the form of plasmid DNA-ligand complexes. The polypeptide was a D-lysine/D-serine copolymer (Lys/Ser = 33/36 or 53/60) modified with...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300868

    authors: Hisayasu S,Miyauchi M,Akiyama K,Gotoh T,Satoh S,Shimada T

    更新日期:1999-04-01 00:00:00

  • Continuous secretion of human soluble CD4 in mice transplanted with genetically modified cells.

    abstract::Somatic transgenesis can be used to confer endogenous production of proteins with therapeutic properties. One such product, recombinant soluble human CD4 (sCD4), has been shown to be an efficient inhibitor of human immunodeficiency virus 1 (HIV-1) in vitro, but its too short half-life in vivo has impaired long-term cl...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:

    authors: Valere T,Bohl D,Klatzmann D,Danos O,Sonigo P,Heard JM

    更新日期:1995-05-01 00:00:00

  • Inhibition of human immunodeficiency virus type 1 by RNA interference using long-hairpin RNA.

    abstract::Inhibition of virus replication by means of RNA interference has been reported for several important human pathogens, including human immunodeficiency virus type 1 (HIV-1). RNA interference against these pathogens has been accomplished by introduction of virus-specific synthetic small interfering RNAs (siRNAs) or DNA ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302786

    authors: Konstantinova P,de Vries W,Haasnoot J,ter Brake O,de Haan P,Berkhout B

    更新日期:2006-10-01 00:00:00

  • Disruption of integrin-dependent adhesion and survival of endothelial cells by recombinant adenovirus expressing isolated beta integrin cytoplasmic domains.

    abstract::We explored the possibility of using a genetic approach to inhibit integrin-mediated endothelial cell adhesion and survival. We constructed recombinant adenoviruses (Ads) expressing chimeric proteins consisting of the cytoplasmic and transmembrane domains of integrin beta1 (CH1), beta3 (CH3) or the beta1 transmembrane...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301236

    authors: Oguey D,George PW,Rüegg C

    更新日期:2000-08-01 00:00:00

  • Gene transfer to adult human lung tissue ex vivo.

    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

    authors: McBride S,Rannie D,Harrison DJ

    更新日期:2000-04-01 00:00:00

  • Towards hematopoietic stem cell-mediated protection against infection with human immunodeficiency virus.

    abstract::The failure of pharmacological approaches to cure infection with the human immunodeficiency virus (HIV) has renewed the interest in gene-based therapies. Among the various strategies that are currently explored, the blockade of HIV entry into susceptible T cells and macrophages promises to be the most powerful interve...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302755

    authors: Schambach A,Schiedlmeier B,Kühlcke K,Verstegen M,Margison GP,Li Z,Kamino K,Bohne J,Alexandrov A,Hermann FG,von Laer D,Baum C

    更新日期:2006-07-01 00:00:00

  • Utility of Epstein-Barr virus-encoded small RNA promoters for driving the expression of fusion transcripts harboring short hairpin RNAs.

    abstract::To induce RNA interference (RNAi), either small interfering RNAs (siRNAs) are directly introduced into the cell or short hairpin RNAs (shRNAs) are expressed from a DNA vector. At present, shRNAs are commonly synthesized by RNA polymerase III (Pol III) promoters of the H1 and U6 RNAs. In this study, we designed and cha...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3303055

    authors: Choy EY,Kok KH,Tsao SW,Jin DY

    更新日期:2008-02-01 00:00:00

  • Efficient gene transfer of VSV-G pseudotyped retroviral vector to human brain tumor.

    abstract::A retroviral vector constructed from the murine leukemia virus (MLV) can only express transgenes in cells undergoing mitosis, indicating its suitability as a delivery vehicle for cancer gene therapy. However, the transduction efficiency (TE) of retroviruses embedding endogenous envelope proteins in human cancer cells ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301390

    authors: Lee H,Song JJ,Kim E,Yun CO,Choi J,Lee B,Kim J,Chang JW,Kim JH

    更新日期:2001-02-01 00:00:00