Cyclodextrin mediated delivery of NF-κB and SRF siRNA reduces the invasion potential of prostate cancer cells in vitro.

Abstract:

:Prostate cancer is the most common cancer in men of the western world. To date, no effective treatment exists for metastatic prostate cancer and consequently, there is an urgent need to develop new and improved therapeutics. In recent years, the therapeutic potential of RNA interference (RNAi) has been extensively explored in a wide range of diseases including prostate cancer using numerous gene delivery vectors. The aims of this study were to investigate the ability of a non-viral modified cyclodextrin (CD) vector to deliver siRNA to the highly metastatic PC-3 prostate cancer cell line, to quantify the resulting knockdown of the two target genes (RelA and SRF) and to study the effects of the silencing on metastasis. Data from a Matrigel in vitro invasion assay indicated that the silencing of the target genes achieved by the CD vector resulted in significant reductions (P=0.0001) in the metastatic potential of these cells. As the silencing of these target genes was shown not to have a negative impact on cell viability, we hypothesise that the mechanism of invasion inhibition is due, in part, to the significant reduction observed (P⩽0.0001) in the level of pro-inflammatory cytokine, MMP9, which is known to be implicated in the metastasis of prostate cancer.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Evans JC,McCarthy J,Torres-Fuentes C,Cryan JF,Ogier J,Darcy R,Watson RW,O'Driscoll CM

doi

10.1038/gt.2015.50

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

802-10

issue

10

eissn

0969-7128

issn

1476-5462

pii

gt201550

journal_volume

22

pub_type

杂志文章
  • Correction: Recent development of AAV-based gene therapies for inner ear disorders.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Gene therapy

    pub_type: 已发布勘误

    doi:10.1038/s41434-020-00186-x

    authors: Lan Y,Tao Y,Wang Y,Ke J,Yang Q,Liu X,Su B,Wu Y,Lin CP,Zhong G

    更新日期:2020-08-01 00:00:00

  • APOBEC3A catabolism of electroporated plasmid DNA in mouse muscle.

    abstract::The mouse is widely used as a model for DNA therapy and vaccination even though the efficiency of DNA delivery in higher mammals and humans is much less. The human APOBEC3 (A3) enzymes impact viral genomes by cytidine deamination, which introduces multiple uridine residues into single-stranded DNA, a process known as ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2014.88

    authors: Kostrzak A,Henry M,Demoyen PL,Wain-Hobson S,Vartanian JP

    更新日期:2015-01-01 00:00:00

  • Excessive activated T-cell proliferation after anti-CD19 CAR T-cell therapy.

    abstract::Excessive activated T-cell proliferation was observed in vivo in one patient after an anti-CD19-chimeric antigen receptor (CAR) T-cell infusion. The patient, who had chemotherapy refractory and CD19+ diffuse large B-cell lymphoma (DLBCL), received an anti-CD19 CAR T-cell infusion following conditioning chemotherapy (f...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41434-017-0001-8

    authors: Zhang WY,Liu Y,Wang Y,Nie J,Guo YL,Wang CM,Dai HR,Yang QM,Wu ZQ,Han WD

    更新日期:2018-06-01 00:00:00

  • Controlled propagation of replication-competent Sindbis viral vector using suicide gene strategy.

    abstract::A major concern of using viral gene therapy is the potential for uncontrolled vector propagation and infection that might result in serious deleterious effects. To enhance the safety, several viral vectors, including vectors based on Sindbis virus, were engineered to lose their capability to replicate and spread after...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2008.153

    authors: Tseng JC,Daniels G,Meruelo D

    更新日期:2009-02-01 00:00:00

  • Intercellular trafficking and enhanced in vivo antitumour activity of a non-virally delivered P27-VP22 fusion protein.

    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

    authors: Zavaglia D,Favrot MC,Eymin B,Tenaud C,Coll JL

    更新日期:2003-02-01 00:00:00

  • Differentiation-specific enhancer activity in transduced keratinocytes: a model for epidermal gene therapy.

    abstract::HaCaT cells, a spontaneously immortalised, nontumorigenic keratinocyte line, were used as a more amenable model than primary keratinocytes for ex vivo-mediated gene transfer. These cells were transduced with retroviral vectors containing the factor IX cDNA under the control of a cytomegaloviral (CMV) promoter/enhancer...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300591

    authors: Page SM,Brownlee GG

    更新日期:1998-03-01 00:00:00

  • Expression of vhs and VP16 during HSV-1 helper virus-free amplicon packaging enhances titers.

    abstract::Recently developed helper virus-free methods of herpes simplex virus (HSV) amplicon vector packaging provide stocks that are virtually devoid of the cytotoxic component normally associated with traditional helper virus-based packaging methods. These approaches involve cotransfection of amplicon plasmid DNA with either...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301340

    authors: Bowers WJ,Howard DF,Brooks AI,Halterman MW,Federoff HJ

    更新日期:2001-01-01 00:00:00

  • Cationic lipid-mediated transfection of cells in culture requires mitotic activity.

    abstract::Cationic lipid-based delivery systems such as lipoplexes or stabilized plasmid-lipid particles (SPLP) represent a safer alternative to viral systems for gene therapy applications. We studied the impact of cell cycle status on the efficiency of transfection of human ovarian carcinoma tumor cells using two cationic-lipi...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300837

    authors: Mortimer I,Tam P,MacLachlan I,Graham RW,Saravolac EG,Joshi PB

    更新日期:1999-03-01 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

  • In utero administration of Ad5 and AAV pseudotypes to the fetal brain leads to efficient, widespread and long-term gene expression.

    abstract::The efficient delivery of genetic material to the developing fetal brain represents a powerful research tool and a means to supply therapy in a number of neonatal lethal neurological disorders. In this study, we have delivered vectors based upon adenovirus serotype 5 (Ad5) and adeno-associated virus (AAV) pseudotypes ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2011.157

    authors: Rahim AA,Wong AM,Ahmadi S,Hoefer K,Buckley SM,Hughes DA,Nathwani AN,Baker AH,McVey JH,Cooper JD,Waddington SN

    更新日期:2012-09-01 00:00:00

  • Novel degradable oligoethylenimine acrylate ester-based pseudodendrimers for in vitro and in vivo gene transfer.

    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

    authors: Russ V,Elfberg H,Thoma C,Kloeckner J,Ogris M,Wagner E

    更新日期:2008-01-01 00:00:00

  • Expression of the human glucocerebrosidase and arylsulfatase A genes in murine and patient primary fibroblasts transduced by an adeno-associated virus vector.

    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:

    authors: Wei JF,Wei FS,Samulski RJ,Barranger JA

    更新日期:1994-07-01 00:00:00

  • Condensation of plasmid DNA with polylysine improves liposome-mediated gene transfer into established and primary muscle cells.

    abstract::Cationic liposomes provide a means to introduce genes into cells both ex vivo and in vivo. In the past few years their use has been described in several tissues, e.g. lungs, liver, endothelium, brain. In this study we evaluated a commercially available poly-cationic liposome formulation in delivering a reporter gene i...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:

    authors: Vitiello L,Chonn A,Wasserman JD,Duff C,Worton RG

    更新日期:1996-05-01 00:00:00

  • Adenoviral gene transfer into the normal and injured spinal cord: enhanced transgene stability by combined administration of temperature-sensitive virus and transient immune blockade.

    abstract::This study characterized gene transfer into both normal and injured adult rat dorsal spinal cord using first (E1-/E3-) or second (E1-/E2A125/E3-, temperature-sensitive; ts) generation of replication-defective adenoviral (Ad) vectors. A novel immunosuppressive regimen aimed at blocking CD4/CD45 lymphocytic receptors wa...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300774

    authors: Romero MI,Smith GM

    更新日期:1998-12-01 00:00:00

  • Antigen design enhances the immunogenicity of Semliki Forest virus-based therapeutic human papillomavirus vaccines.

    abstract::Cellular immunity against cancer can be achieved with viral vector- and DNA-based immunizations. In preclinical studies, cancer vaccines are very potent, but in clinical trials these potencies are not achieved yet. Thus, a rational approach to improve cancer vaccines is warranted. We previously demonstrated that the r...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2015.24

    authors: Ip PP,Boerma A,Walczak M,Oosterhuis K,Haanen JB,Schumacher TN,Nijman HW,Daemen T

    更新日期:2015-07-01 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

  • Identification of polyamides that enhance adenovirus-mediated gene expression in the urothelium.

    abstract::Adenovirus-mediated gene therapy of bladder diseases has been limited by the inability to transduce the urothelium successfully using adenoviral vectors. We have sought to identify agents that would increase adenovirus-mediated transgene expression in the bladder. We have utilized a rat model to screen compounds for t...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301348

    authors: Connor RJ,Engler H,Machemer T,Philopena JM,Horn MT,Sutjipto S,Maneval DC,Youngster S,Chan TM,Bausch J,McAuliffe JP,Hindsgaul O,Nagabhushan TL

    更新日期:2001-01-01 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

  • A dual chain chimeric antigen receptor (CAR) in the native antibody format for targeting immune cells towards cancer cells without the need of an scFv.

    abstract::Adoptive cell therapy with chimeric antigen receptor (CAR)-modified T cells showed remarkable therapeutic efficacy in the treatment of leukaemia/lymphoma. However, the application to a variety of cancer entities is often constricted by the non-availability of a single chain antibody (scFv), which is usually the target...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2016.48

    authors: Faitschuk E,Nagy V,Hombach AA,Abken H

    更新日期:2016-10-01 00:00:00

  • PDGF-B gene therapy accelerates bone engineering and oral implant osseointegration.

    abstract::Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired chronic wounds such as diabetic ulcers and periodontal lesions. However, limitations in predictability of tissue regeneration occur due, in part, to transient growth factor bioavailability in vivo. Here, we report that gene delivery of P...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2009.117

    authors: Chang PC,Seol YJ,Cirelli JA,Pellegrini G,Jin Q,Franco LM,Goldstein SA,Chandler LA,Sosnowski B,Giannobile WV

    更新日期:2010-01-01 00:00:00

  • Inside out: optimization of lipid nanoparticle formulations for exterior complexation and in vivo delivery of saRNA.

    abstract::Self-amplifying RNA (saRNA) is a promising biotherapeutic tool that has been used as a vaccine against both infectious diseases and cancer. saRNA has been shown to induce protein expression for up to 60 days and elicit immune responses with lower dosing than messenger RNA (mRNA). Because saRNA is a large (~9500 nt), n...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41434-019-0095-2

    authors: Blakney AK,McKay PF,Yus BI,Aldon Y,Shattock RJ

    更新日期:2019-09-01 00:00:00

  • A new plasmid-based microRNA inhibitor system that inhibits microRNA families in transgenic mice and cells: a potential new therapeutic reagent.

    abstract::Current tools for the inhibition of microRNA (miR) function are limited to modified antisense oligonucleotides, sponges and decoy RNA molecules and none have been used to understand miR function during development. CRISPR/Cas-mediated deletion of miR sequences within the genome requires multiple chromosomal deletions ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2016.22

    authors: Cao H,Yu W,Li X,Wang J,Gao S,Holton NE,Eliason S,Sharp T,Amendt BA

    更新日期:2016-06-01 00:00:00

  • Species differences in transgene DNA uptake in hepatocytes after adenoviral transfer correlate with the size of endothelial fenestrae.

    abstract::Sinusoidal fenestrae may restrict the transport of gene transfer vectors according to their size. Using Vitrobot technology and cryo-electron microscopy, we show that the diameter of human adenoviral serotype 5 vectors is 93 nm with protruding fibers of 30 nm. Thus, a diameter of fenestrae of 150 nm or more is likely ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302899

    authors: Snoeys J,Lievens J,Wisse E,Jacobs F,Duimel H,Collen D,Frederik P,De Geest B

    更新日期:2007-04-01 00:00:00

  • Schwann cell targeting via intrasciatic injection of AAV8 as gene therapy strategy for peripheral nerve regeneration.

    abstract::Efficient transduction of the peripheral nervous system (PNS) is required for gene therapy of acquired and inherited neuropathies, neuromuscular diseases and for pain treatment. We have characterized the tropism and transduction efficiency of different adeno-associated vectors (AAV) pseudotypes after sciatic nerve inj...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2011.7

    authors: Homs J,Ariza L,Pagès G,Udina E,Navarro X,Chillón M,Bosch A

    更新日期:2011-06-01 00:00:00

  • Mechanism of lipoplex gene delivery in mouse lung: binding and internalization of fluorescent lipid and DNA components.

    abstract::We introduce a lung inflation-fixation protocol to examine the distribution and gene transfer efficiency of fluorescently tagged lipoplexes using fluorescence confocal microscopy within thick lung tissue sections. Using this technique, we tested the hypothesis that factors related to lipoplex distribution were the pre...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301461

    authors: Uyechi LS,Gagné L,Thurston G,Szoka FC Jr

    更新日期:2001-06-01 00:00:00

  • Efficient tuberculosis treatment in mice using chemotherapy and immunotherapy with the combined DNA vaccine encoding Ag85B, MPT-64 and MPT-83.

    abstract::Although most cases of tuberculosis (TB) can be cured with antibiotics, relapse is common if patients do not continue chemotherapy for at least 6 months. Thus, improved therapeutic strategies are urgently needed. We previously found that the combined DNA vaccine encoding the Mycobacterium tuberculosis proteins Ag85B, ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2008.13

    authors: Yu DH,Hu XD,Cai H

    更新日期:2008-05-01 00:00:00

  • Combined ionizing radiation and sKDR gene delivery for treatment of prostate carcinomas.

    abstract::Overexpression of vascular endothelial growth factor (VEGF) and its cognate receptor KDR has been linked to a more aggressive phenotype of human prostate carcinomas. The importance of signal transduction through the VEGF receptor 2 is illustrated by use of soluble KDR, which binds to VEGF and sequesters this ligand be...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302432

    authors: Kaliberov SA,Kaliberova LN,Buchsbaum DJ

    更新日期:2005-03-01 00:00:00

  • IL-12 plasmid-enhanced DNA vaccination against carcinoembryonic antigen (CEA) studied in immune-gene knockout mice.

    abstract::Intramuscular (i.m.) injection of a plasmid encoding human carcinoembryonic antigen (CEA) elicited immunity against transplanted syngeneic (C57BL/6) CEA-positive Lewis lung carcinoma (CEA/LLC) cells, but tumors still appeared in all mice. In wild-type mice, coinjection of an IL-12 plasmid markedly enhanced anti-CEA hu...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301274

    authors: Song K,Chang Y,Prud'homme GJ

    更新日期:2000-09-01 00:00:00

  • Foamy viral vector integration sites in SCID-repopulating cells after MGMTP140K-mediated in vivo selection.

    abstract::Foamy virus (FV) vectors are promising for hematopoietic stem cell (HSC) gene therapy but preclinical data on the clonal composition of FV vector-transduced human repopulating cells is needed. Human CD34(+) human cord blood cells were transduced with an FV vector encoding a methylguanine methyltransferase (MGMT)P140K ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2015.20

    authors: Olszko ME,Adair JE,Linde I,Rae DT,Trobridge P,Hocum JD,Rawlings DJ,Kiem HP,Trobridge GD

    更新日期:2015-07-01 00:00:00

  • Baculovirus-mediated periadventitial gene transfer to rabbit carotid artery.

    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

    authors: Airenne KJ,Hiltunen MO,Turunen MP,Turunen AM,Laitinen OH,Kulomaa MS,Ylä-Herttuala S

    更新日期:2000-09-01 00:00:00