Abstract:
:Small interfering RNAs (siRNAs) are emerging as promising therapeutic tools. However, the widespread clinical application of such molecules as modulators of gene expression is still dependent on several aspects that limit their bioavailability. One of the most promising strategies to overcome the barriers faced by gene silencing molecules involves the use of lipid-based nanoparticles (LNPs) and viral vectors, such as adenoviruses (Ads). The primary obstacle for translating gene silencing technology from an effective research tool into a feasible therapeutic strategy remains its efficient delivery to the targeted cell type in vivo. In this study, we tested the capability of LNPs and Ad to transduce and treat locally tumors in vivo. Efficient knockdown of a surrogate reporter (luciferase) and therapeutic target genes such as the kinesin spindle protein (KIF11) and polo-like kinase 1 were observed. Most importantly, this activity led to a cell cycle block as a consequence and slowed down tumor progression in tumor-bearing animals. Our data indicate that it is possible to achieve tumor transduction with si/short hairpin RNAs and further improve the delivery strategy that likely in the future will lead to the ideal non-viral particle for targeted cancer gene silencing.
journal_name
Gene Therjournal_title
Gene therapyauthors
Dharmapuri S,Peruzzi D,Marra E,Palombo F,Bett AJ,Bartz SR,Yong M,Ciliberto G,La Monica N,Buser CA,Toniatti C,Aurisicchio Ldoi
10.1038/gt.2011.27subject
Has Abstractpub_date
2011-07-01 00:00:00pages
727-33issue
7eissn
0969-7128issn
1476-5462pii
gt201127journal_volume
18pub_type
杂志文章相关文献
GENE THERAPY文献大全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
更新日期:1999-10-01 00:00:00
abstract::As soon as RNA interference (RNAi) was found to work in mammalian cells, research quickly focused on harnessing this powerful endogenous and specific mechanism of gene silencing for human therapy. RNAi uses small RNAs, less than 30 nucleotides in length, to suppress expression of genes with complementary sequences. Tw...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302703
更新日期:2006-03-01 00:00:00
abstract::A highly desirable feature for an human immunodeficiency virus type 1 (HIV-1) vaccine is the ability to induce broadly reactive anti-envelope antibodies that can neutralize primary HIV-1 isolates. Two immunizations with an HIV-1 envelope-encoding plasmid together with recombinant granulocyte-macrophage colony-stimulat...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302275
更新日期:2004-07-01 00:00:00
abstract::More than one hundred different mutations in the gene encoding rhodopsin are associated with a group of retinal degenerations including retinitis pigmentosa, congenital stationary night blindness and retinitis punctata albescens. Given this large heterogeneity of mutations, it would be ideal to develop mutation-indepe...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302512
更新日期:2005-08-01 00:00:00
abstract::Adeno-associated virus (AAV)-mediated gene delivery systems have been shown to be effective tools for gene manipulation in the inner ear. For example, hair cells (HCs) and multiple other cell types can be transduced by the local injection of AAVs into the inner ear. However, application of the AAV-mediated CRISPR/Cas9...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/s41434-020-0124-1
更新日期:2020-08-01 00:00:00
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
更新日期:1999-03-01 00:00:00
abstract::Despite significant advances in basic research, the treatment of degenerative diseases of the nervous system remains one of the greatest challenges for translational medicine. The childhood onset motor neuron disorder spinal muscular atrophy (SMA) has been viewed as one of the more tractable targets for molecular ther...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/gt.2017.52
更新日期:2017-09-01 00:00:00
abstract::Deficiency in acid alpha-D-glucosidase results in Pompe's disease. Modified single-stranded oligonucleotide (ODN) was designed to correct the acid alpha-D-glucosidase gene with a C1935 --> A (Asp --> Glu) point mutation which causes a complete loss of enzymatic activity for glycogen digestion in the lysosome. The ODN ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302096
更新日期:2003-10-01 00:00:00
abstract::Citrullinemia is an autosomal recessive disorder caused by the deficiency of argininosuccinate synthetase (AS). It is characterized by elevated levels of blood citrulline and ammonia, which often results in hyperammonemic coma and early neonatal death in affected children. We have explored the use of adenoviral vector...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301303
更新日期:2000-10-01 00:00:00
abstract::Aptamers are oligonucleotides evolved in vitro or in nature to bind target ligands with high affinity and specificity. They are emerging as powerful tools in the fields of therapeutics, drug development, target validation and diagnostics. Aptamers are attractive alternatives to antibody- and small-molecule-based thera...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302900
更新日期:2007-02-01 00:00:00
abstract::Because periodontal ligament (PDL) cells are reported to contain progenitor or stem cell populations, they are considered a beneficial cell source for clinical periodontal regeneration. Both bone morphogenetic protein 4 (BMP4) and human telomerase reverse transcriptase (hTERT) have essential roles in the modulation of...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.158
更新日期:2011-05-01 00:00:00
abstract::Episomally maintained self-replicating systems present attractive alternative vehicles for gene therapy applications. Recent insights into the ability of chromosomal scaffold/matrix attachment regions (S/MARs) to mediate episomal maintenance of genetic elements allowed the development of a small circular episomal vect...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302593
更新日期:2006-01-01 00:00:00
abstract::Glucagon-like peptide 1 (GLP-1) is released from neuroendocrine cells in the intestine in the postprandial state and augments glucose-stimulated insulin secretion from pancreatic beta cells. To develop non-beta cells that exhibit physiologically regulated insulin secretion, we coexpressed the GLP-1 receptor and human ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302055
更新日期:2003-09-01 00:00:00
abstract::This work demonstrates that electrical muscle stimulation markedly increases the transfection efficiency of an intramuscular injection of plasmid DNA. In soleus or extensor digitorum longus muscles of adult rats the percentage of transfected fibers increased from about 1 to more than 10. The number of transfected fibe...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300847
更新日期:1999-04-01 00:00:00
abstract::The canine is the most important large animal model for testing novel hemophilia A (HA) treatment. It is often necessary to use canine factor VIII (cFIII) gene or protein for the evaluation of HA treatment in the canine model. However, different biological properties between cFVIII and human FVIII (hFVIII) indicated t...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2016.34
更新日期:2016-07-01 00:00:00
abstract::Human adenovirus (Ad) vectors are extensively used as gene transfer vehicles. However, a serious obstacle for the use of these vectors in clinical applications is due to pre-existing immunity to human Ads affecting the efficacy of gene transfer. One of the approaches to circumvent host immune response could be the dev...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302146
更新日期:2004-01-01 00:00:00
abstract::The accessibility of adipose tissue and its ability to secrete various bioactive molecules suggest that adipose cells may be attractive targets for gene therapy applications. Here, we report the use of highly defective herpes simplex virus (HSV) vectors as suitable gene transfer agents for adipose cells in culture and...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302359
更新日期:2005-01-01 00:00:00
abstract::Defensins are small cationic proteins that harbor broad-spectrum microbicidal activity against bacteria, fungi and viruses. This study examines the effects on pathogens of the epidermis engineered to express human beta-defensin 3 (HBD3) to combat bacterial infections. First, we examined the localization of HBD3 in the...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302472
更新日期:2005-05-01 00:00:00
abstract::We have tested the cationic liposome N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethyl-ammoniummethylsul phate, (DOTAP), for gene delivery in vitro and in vivo with a view to clinical use in gene therapy for cystic fibrosis. Delivery of lacZ cDNA-DOTAP complexes via aerosol showed promoter-dependent differences in the pat...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1995-11-01 00:00:00
abstract::Advances in islet transplantation have encouraged efforts to create alternative insulin-secreting cells that overcome limitations associated with current therapies. We have recently demonstrated durable correction of murine and porcine diabetes by syngeneic and autologous implantation, respectively, of primary hepatoc...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.12
更新日期:2010-05-01 00:00:00
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
更新日期:2018-06-01 00:00:00
abstract::X-linked chronic granulomatous disease (X-CGD) is an inherited immunodeficiency with absent phagocyte NADPH-oxidase activity caused by defects in the gene-encoding gp91(phox). Here, we evaluated strategies for less intensive conditioning for gene therapy of genetic blood disorders without selective advantage for gene ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.96
更新日期:2009-12-01 00:00:00
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
更新日期:2002-08-01 00:00:00
abstract::To elucidate further the potential of a Semliki Forest virus (SFV) vector in vivo for gene therapy, we constructed a vector, SFV-IL12, to transfer murine IL-12 genes into tumors. A single intratumoral injection of established B16 murine melanoma with SFV-IL12 resulted in a significant inhibition of tumor growth, while...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300841
更新日期:1999-04-01 00:00:00
abstract::Mutations in GJB2, which codes for the gap junction (GJ) protein connexin26 (Cx26), are the most common causes of human nonsyndromic hereditary deafness. We inoculated modified adeno-associated viral (AAV) vectors into the scala media of early postnatal conditional Gjb2 knockout mice to drive exogenous Cx26 expression...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2013.59
更新日期:2014-01-01 00:00:00
abstract::Previous studies have demonstrated that antigen-specific tolerance could be induced by lipopolysaccharide (LPS)-stimulated B cells retrovirally transduced with an immunoglobulin-antigen (or epitope-containing peptide) fusion construct. To investigate the mechanism of this gene therapy system, we now adapted this appro...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302327
更新日期:2004-10-01 00:00:00
abstract::We report on systemic delivery and long-term biological effects of apolipoprotein E (apoE) obtained by intramuscular (i.m.) plasmid DNA injection. ApoE plays an important role in lipoprotein catabolism and apoE knock-out mice develop severe hypercholesterolemia and diffuse atherosclerosis. We have injected apoE-defici...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301310
更新日期:2000-11-01 00:00:00
abstract::Sindbis virus expression has been used for in vitro investigations of antigen processing, presentation and epitope mapping. The recent development of a replication-deficient recombinant Sindbis virus expression vector has made in vivo expression possible with minimal pathogenic risk. Advantages of Sindbis virus over o...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300458
更新日期:1997-08-01 00:00:00
abstract::Oligonucleotides (ODNs) show great promise in their ability to specifically inhibit single gene expression but must cross the cell membrane, escape the endosomal vesicle, and possibly traverse the nuclear membrane to arrive at their intracellular target molecules. In an attempt to improve the delivery of phosphodieste...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-04-01 00:00:00
abstract::Gene transfer to airway epithelia with amphotropic pseudotyped retroviral vectors is inefficient following apical vector application. To better understand this inefficiency, we localized the expression of Pit2, the amphotropic receptor, in polarized human airway epithelia. Pit2 was expressed on both the apical and bas...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301714
更新日期:2002-07-01 00:00:00