Reduction of fibronectin expression by intravitreal administration of antisense oligonucleotides

Roy, Sayon; Zhang, Kathy; Roth, Timothy P.; Vinogradov, Sergei A.; Kao, Richard; Kabanov, Alexander V.

doi:10.1038/8654

Cited by 58 publications

(43 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…23 This approach was used, for example, with antisense oligonucleotides to produce stable complexes dispersed in aqueous media that revealed high activity in regulating gene expression in in vitro and in vivo studies. 7,14,15 Also, the formation of dispersed complexes from plasmid DNA and PEO-modified poly-l-lysine has been well documented. 8,10,12 However, there is relatively little data on the transfection activity of these systems in vitro, 8,12 and we are not aware of any paper reporting performance of these systems in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9][10][11][12][13] Furthermore, increased activity of antisense oligonucleotides incorporated into such systems was reported based on in vitro and in vivo studies. 7,14,15 However, few improvements of transfection activity of plasmid DNA were reported. Furthermore, these systems have not been compared with commercially available transfection agents, such as PEI, dendrimers, or cationic liposomes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of polyether-polyethyleneimine graft copolymers as gene transfer agents

et al. 2000

View full text Add to dashboard Cite

Cationic copolymers consisting of polycations linked to nonionic polymers are evaluated as non-viral gene delivery systems. These copolymers are known to produce soluble complexes with DNA, but only a few studies have characterized the transfection activity of these complexes. This work reports the synthesis and characterization of a series of cationic copolymers obtained by grafting the polyethyleneimine (PEI) with non-ionic polyethers, poly (ethylene oxide) (PEO) or Pluronic 123 (P123). The PEO-PEI conjugates differ in the molecular mass of PEI (2 kDa and 25 kDa) and the degree of modification of PEI with PEO. All of these conjugates form complexes upon mixing with plasmids, which are stable in aqueous dispersion for several days. The sizes of the particles formed in these systems vary from 70 to 200 nm depending on the composition of the complex. How-

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of polyether-polyethyleneimine graft copolymers as gene transfer agents

et al. 2000

View full text Add to dashboard Cite

show abstract

“…In previous studies we have documented that intravitreal administration of fibronectin antisense oligos reduced fibronectin synthesis in the retinal vascular cells (22). With this strategy in place, we determined whether reduction of fibronectin overexpression would prevent the development of vascular BM thickening in diabetic retinopathy.…”

mentioning

confidence: 99%

Downregulation of Fibronectin Overexpression Reduces Basement Membrane Thickening and Vascular Lesions in Retinas of Galactose-Fed Rats

et al. 2003

Self Cite

View full text Add to dashboard Cite

Overexpression of extracellular matrix (ECM) components is closely associated with the development of vascular basement membrane (BM) thickening, a histological hallmark of diabetic microangiopathy. To determine whether BM thickening of retinal capillaries could be prevented by down regulating synthesis of fibronectin, an ECM component, we used antisense oligos targeted against translation initiation site of the fibronectin transcript in galactose-fed rat, an animal model of diabetic retinopathy. After 2 months of galactose-feeding, intravitreal administration of 3 mol/l antisense fibronectin oligos was initiated at monthly intervals for 3 months. The antisense strategy significantly reduced fibronectin mRNA and protein level in the retinas of treated eyes compared with untreated eyes of galactose-fed rats (130 ؎ 16 vs. 179 ؎ 18% of control, P < 0.01, and 144 ؎ 28 vs. 204 ؎ 22% of control, respectively, r ‫؍‬ 0.9) and resulted in partial reduction of retinal capillary BM width (123 ؎ 16 vs. 201 ؎ 12 nm, P < 0.03). In eyes treated with antisense fibronectin oligos, ϳ35% reduction in both pericyte loss and acellular retinal capillaries was observed (P < 0.04 and P < 0.03, respectively). Glycohemoglobin level was consistently elevated in the treated (6.9 ؎ 0.6%) and untreated (6.5 ؎ 0.7%) galactose-fed rats compared with control rats (4.5 ؎ 0.8%). Overall, these results indicate that downregulation of fibronectin synthesis reduces BM thickening in retinal capillaries with beneficial effect to retinal lesions. The antisense fibronectin oligos may provide a useful approach for reducing vascular lesions in diabetic retinopathy. The thickened vascular BM may be a potential therapeutic target for preventing retinal lesions in diabetic retinopathy. Diabetes 52: 1229 -1234, 2003

show abstract

“…Furthermore, they can release solutes upon change of environmental conditions such as pH (acidification), concentration, and chemical structure of elementary salt (Solomatin et al 2003;Oh et al 2006). These nanomaterials were shown to efficiently deliver DNA molecules in vitro and in vivo (Roy et al 1999;Nguyen et al 2000;Harada-Shiba et al 2002;Junghans et al 2005), and were used to stabilize enzymes for cellmediated drug delivery discussed in the next section. Nanogels are another novel class of nanomaterials proposed in our laboratories for drug delivery (Vinogradov et al 2002).…”

Section: Nanomaterials For Drug Delivery Across the Blood-brain Barriermentioning

confidence: 99%

Novel Nanomaterials for Clinical Neuroscience

Gilmore

Xiang

Quan

et al. 2008

J Neuroimmune Pharmacol

205

123

View full text Add to dashboard Cite

Neurodegenerative disorders including Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, and stroke are rapidly increasing as population ages. The field of nanomedicine is rapidly expanding and promises revolutionary advances to the diagnosis and treatment of devastating human diseases. This paper provides an overview of novel nanomaterials that have potential to improve diagnosis and therapy of neurodegenerative disorders. Examples include liposomes, nanoparticles, polymeric micelles, block ionomer complexes, nanogels, and dendrimers that have been tested clinically or in experimental models for delivery of drugs, genes, and imaging agents. More recently discovered nanotubes and nanofibers are evaluated as promising scaffolds for neuroregeneration. Novel experimental neuroprotective strategies also include nanomaterials, such as fullerenes, which have antioxidant properties to eliminate reactive oxygen species in the brain to mitigate oxidative stress. Novel technologies to enable these materials to cross the blood brain barrier will allow efficient systemic delivery of therapeutic and diagnostic agents to the brain. Furthermore, by combining such nanomaterials with cell-based delivery strategies, the outcomes of neurodegenerative disorders can be greatly improved.

show abstract

Reduction of fibronectin expression by intravitreal administration of antisense oligonucleotides

Cited by 58 publications

References 19 publications

Evaluation of polyether-polyethyleneimine graft copolymers as gene transfer agents

Evaluation of polyether-polyethyleneimine graft copolymers as gene transfer agents

Downregulation of Fibronectin Overexpression Reduces Basement Membrane Thickening and Vascular Lesions in Retinas of Galactose-Fed Rats

Novel Nanomaterials for Clinical Neuroscience

Contact Info

Product

Resources

About