Abstract:
:Choroidal neovascularization (CNV) leads to loss of vision in age-related macular degeneration (AMD), the leading cause of blindness in adult population over 50 years old. In this study, we developed intravenously administered, nanoparticulate, targeted nonviral retinal gene delivery systems for the management of CNV. CNV was induced in Brown Norway rats using a 532 nm laser. We engineered transferrin, arginine-glycine-aspartic acid (RGD) peptide or dual-functionalized poly-(lactide-co-glycolide) nanoparticles to target delivery of anti-vascular endothelial growth factor (VEGF) intraceptor plasmid to CNV lesions. Anti-VEGF intraceptor is the only intracellularly acting VEGF inhibitory modality. The results of the study show that nanoparticles allow targeted delivery to the neovascular eye but not the control eye on intravenous administration. Functionalizing the nanoparticle surface with transferrin, a linear RGD peptide or both increased the retinal delivery of nanoparticles and subsequently the intraceptor gene expression in retinal vascular endothelial cells, photoreceptor outer segments and retinal pigment epithelial cells when compared to nonfunctionalized nanoparticles. Most significantly, the CNV areas were significantly smaller in rats treated with functionalized nanoparticles as compared to the ones treated with vehicle or nonfunctionalized nanoparticles. Thus, surface-functionalized nanoparticles allow targeted gene delivery to the neovascular eye on intravenous administration and inhibit the progression of laser-induced CNV in a rodent model.
journal_name
Gene Therjournal_title
Gene therapyauthors
Singh SR,Grossniklaus HE,Kang SJ,Edelhauser HF,Ambati BK,Kompella UBdoi
10.1038/gt.2008.185subject
Has Abstractpub_date
2009-05-01 00:00:00pages
645-59issue
5eissn
0969-7128issn
1476-5462pii
gt2008185journal_volume
16pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract::The potential for gene therapy to be an effective treatment for cystic fibrosis has been hampered by the limited gene transfer efficiency of current vectors. We have shown that recombinant Sendai virus (SeV) is highly efficient in mediating gene transfer to differentiated airway epithelial cells, because of its capaci...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302991
更新日期:2007-10-01 00:00:00
abstract::Cancer therapies that target a single protein or pathway may be limited by their specificity, thus missing key players that control cellular proliferation and contributing to the failure of the treatment. We propose that approaches to cancer therapy that hit multiple targets would limit the chances of escape. To this ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/s41434-019-0096-1
更新日期:2020-02-01 00:00:00
abstract::Intraperitoneal (i.p.) recurrence of cisplatin-refractory and p53 mutant ovarian cancer is a major clinical problem, despite surgery and chemotherapy. dl1520 (ONYX-015) is an E1B-55 kDa gene-deleted adenovirus engineered selectively to replicate in and destroy cancer cells lacking functional p53. However, a correlatio...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301319
更新日期:2000-11-01 00:00:00
abstract::For successful cancer gene therapy via intravenous (i.v.) administration, it is essential to optimize the stability of carriers in the systemic circulation and the cellular association after the accumulation of the carrier in tumor tissue. However, a dilemma exists regarding the use of poly(ethylene glycol) (PEG), whi...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302843
更新日期:2007-01-01 00:00:00
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
更新日期:2001-01-01 00:00:00
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
更新日期:1999-05-01 00:00:00
abstract::Confinement of transgene expression to target cells is highly desirable in gene therapy. Current strategies of transcriptional targeting to tumors usually rely on tissue-specific promoters to control gene expression. However, such promoters generally have much lower activity than the constitutive viral promoters. We h...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302029
更新日期:2003-08-01 00:00:00
abstract::RNA interference (RNAi) was reported to block hepatitis B virus (HBV) gene expression and replication in vitro and in vivo. However, it remains a technical challenge for RNAi-based therapy to achieve long-term and complete inhibition effects in chronic HBV infection, which presumably requires more extensive and unifor...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302846
更新日期:2007-01-01 00:00:00
abstract::Nonhealing bone defects are difficult to treat. As the bone morphogenic protein and transforming growth factor beta pathways have been implicated in bone healing, we hypothesized that percutaneous Smad7 silencing would enhance signaling through both pathways and improve bone formation. Critical sized parietal trephine...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2013.15
更新日期:2013-09-01 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::Retroviral vectors are being used increasingly in clinical gene therapy protocols but low transduction frequencies are presenting a significant obstacle to progress. In this paper we report a simple method to enhance the efficiency of ex vivo retroviral gene transfer. Calcium chloride is added to the vector stock and ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
abstract::Rescue of dystrophic skeletal muscle in mdx and utrophin/dystrophin-deficient (dko) mouse models by reintroduction of dystrophin has validated gene therapy as a potential therapeutic approach for Duchenne muscular dystrophy. However, the size of the dystrophin gene exceeds the capacity of adeno-associated viral (AAV) ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302686
更新日期:2006-05-01 00:00:00
abstract::Breast cancer is the leading cancer diagnosed in women and the second leading cause of cancer-related deaths in women. Current limitations to standard chemotherapy in the clinic are extensively researched, including problems arising from repeated treatments with the same drugs. The phenomenon that cancer cells become ...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/gt.2016.67
更新日期:2016-12-01 00:00:00
abstract::In 2012, we reported that 5 out of 11 subjects in a clinical trial (NCT00372320) administering AdhAQP1 to radiation-damaged parotid glands showed increased saliva flow rates and decreased symptoms over the initial 42 days. AdhAQP1 is a first-generation, E1-deleted, replication-defective, serotype 5 adenoviral vector e...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2015.55
更新日期:2015-09-01 00:00:00
abstract::The structure of 'stabilized plasmid-lipid particles' (SPLP) and their properties as systemic gene therapy vectors has been investigated. We show that SPLP can be visualized employing cryo-electron microscopy to be homogeneous particles of diameter 72 +/- 5 nm consisting of a lipid bilayer surrounding a core of plasmi...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301308
更新日期:2000-11-01 00:00:00
abstract::This study examines the clinical relevance of tissue engineering integrating gene therapy and polymer science to bone regeneration. Bilateral maxillary defects (3 x 1.2 cm(2)) in 20 miniature swine were bridged with a bioresorbable internal splint. Constructs were created using ex vivo adenovirus bone morphogenetic pr...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302106
更新日期:2003-11-01 00:00:00
abstract::Many retroviral vectors based on murine leukaemia virus (MLV) contain the first 420 nucleotides of the gag gene, as this was reported to increase vector titre by increasing the efficiency of RNA packaging. In this study, deletion of this gag sequence from its original location did not decrease the titre of two retrovi...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301081
更新日期:2000-02-01 00:00:00
abstract::Urothelial bladder cancer is the most common malignancy of the urinary tract. Although most cases are initially diagnosed as non-muscle-invasive, more than 80% of patients will develop recurrent or metastatic tumors. No effective therapy exists currently for late-stage metastatic tumors. By intravesical application, l...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2016.18
更新日期:2016-05-01 00:00:00
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 exp...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2015.50
更新日期:2015-10-01 00:00:00
abstract::Newly isolated serotypes of AAV readily cross the endothelial barrier to provide efficient transgene delivery throughout the body. However, tissue-specific expression is preferred in most experimental studies and gene therapy protocols. Previous efforts to restrict gene expression to the myocardium often relied on dir...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.105
更新日期:2011-01-01 00:00:00
abstract::With the long-term goal of developing a gene-based treatment for osteoarthritis (OA), we performed studies to evaluate the equine joint as a model for adeno-associated virus (AAV)-mediated gene transfer to large, weight-bearing human joints. A self-complementary AAV2 vector containing the coding regions for human inte...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2012.81
更新日期:2013-06-01 00:00:00
abstract::Efficient gene delivery is a critical obstacle for gene therapy that must be overcome. Until current limits of gene delivery technology are solved, identification of systems with bystander effects is highly desirable. As an anticancer agent, radioactive iodine (131)I has minimal toxicity. The physical characteristics ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302758
更新日期:2006-07-01 00:00:00
abstract::The proteasome is a multisubunit cytosolic protein complex responsible for degrading cytosolic proteins. Several studies have implicated its involvement in the processing of viral particles used for gene delivery, thereby limiting the efficiency of gene transfer. Peptide-based nonviral gene delivery systems are suffic...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302575
更新日期:2005-11-01 00:00:00
abstract::Cancer cachexia, characterized by anorexia, weight loss and progressive tissue wasting, has been postulated to be mediated by various cytokines. However, the precise mechanism of cachexia induction is not fully explained. We have developed synthetic double-stranded oligodeoxynucleotides (ODN) as 'decoy' cis-elements t...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300819
更新日期:1999-01-01 00:00:00
abstract::To achieve high transgene expression in the liver, we have compared the reporter gene expression among various murine retroviral long terminal repeats (LTRs) or leader sequences in vitro. Transient reporter gene expression assays revealed the highest gene expression by the polycythemic strain of spleen focus-forming v...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301655
更新日期:2002-02-01 00:00:00
abstract::Coagulation factor X (FX)-binding ablated adenovirus type 5 (Ad5) vectors have been genetically engineered to ablate the interaction with FX, resulting in substantially reduced hepatocyte transduction following intravenous administration in rodents. Here, we quantify viral genomes and gene transfer mediated by Ad5 and...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2011.87
更新日期:2012-01-01 00:00:00
abstract::Hypoxia initiates an adaptive physiological response in all organisms and plays a role in the pathogenesis of several human diseases. The hypoxia/HIF-inducible factor-1 (HIF-1) transcription factor mediates transcriptional responses to hypoxia by binding to a cis-acting hypoxia-responsive element (HRE) present within ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301605
更新日期:2001-12-01 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::Radiosensitization of human gastrointestinal tumors by 5-fluorouracil (5-FU) has been studied in vitro and clinically in human cancer therapy trials. The bacterial enzyme cytosine deaminase (CD) converts the nontoxic prodrug 5-fluorocytosine (5-FC) into 5-FU. Human colon cancer cells stably expressing CD have been sho...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301196
更新日期:2000-06-01 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