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Черников, В. Г.; Terekhov, S. M.; Krokhina, T. B.; Shishkin, S. S.; Смирнова, Т. Д.; Adnoral, N. V.; Rebrov, L. B.; Denisov-Nikol'skii, Yu. I.; Bykov, B. A.

doi:10.1023/a:1012314921787

Cited by 6 publications

(7 citation statements)

References 2 publications

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“…26 To assess whether the compounds 7 and 8 retain similar properties, we determined comparative cell toxicity of 1, 2, 7, 8, G418 and gentamicin in HEK-293 cells ( Table 1). The LC 50 values obtained for 7 and 8 (25.8 and 7 mM) were similar to those for 1 and 2 (21.4 and 6.1 mM), and were 10-and 2.8-fold higher than that of the clinical aminoglycoside gentamicin (LC 50 = 2.5 mM) Among all aminoglycosides tested the aminoglycoside antibiotic G418, which is known as one of the most cytotoxic aminoglycoside, 33 exhibited the lowest LC 50 value (1.3 mM).…”

Section: Comparative Stop Codon Suppression Tests In Mammalian Cell Linesupporting

confidence: 59%

“…Third, despite its potent readthrough activity, the use of G418 as a therapeutic agent is not possible because it is lethal even at very low concentrations. 33 Figure 1. Chemical structures of a series of natural and synthetic 2-deoxystreptamine-derived (ring II) aminoglycosides, including compounds 1-8 that were investigated in this study.…”

Section: Design Hypotheses and Synthesismentioning

confidence: 99%

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Repairing faulty genes by aminoglycosides: Development of new derivatives of geneticin (G418) with enhanced suppression of diseases-causing nonsense mutations

Nudelman

Glikin

Smolkin

et al. 2010

Bioorganic & Medicinal Chemistry

117

130

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Section: Comparative Stop Codon Suppression Tests In Mammalian Cell Linesupporting

confidence: 59%

Section: Design Hypotheses and Synthesismentioning

confidence: 99%

Repairing faulty genes by aminoglycosides: Development of new derivatives of geneticin (G418) with enhanced suppression of diseases-causing nonsense mutations

Nudelman

Glikin

Smolkin

et al. 2010

Bioorganic & Medicinal Chemistry

117

130

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“…250 ppm, did not introduce any cytotoxic effect on the osteoblast‐like human cells. In fact, it has been reported that the dose that kills half of the cellular population tested (LD50) for gentamicin ranges from 2 000 to 3 500 ppm for the most sensitive and resistant cells, respectively 36. Furthermore, all the PLA fibers presented relatively similar values in terms of biocompatibility.…”

Section: Resultsmentioning

confidence: 95%

Controlled Delivery of Gentamicin Antibiotic from Bioactive Electrospun Polylactide‐Based Ultrathin Fibers

Torres‐Giner¹,

Martínez‐Abad²,

Gimeno-Alcañíz

et al. 2011

Adv Eng Mater

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The purpose of this study was to generate ultrathin fibers based on polylactide (PLA) biopolyester with antimicrobial controlled release capacity to treat bacterial infections. To achieve this objective, gentamicin antibiotic was encapsulated into pure PLA fibers, a blend of PLA–collagen and coaxial fibers containing a skin of PLA and a core of collagen using the electrospinning technique. The morphology of the gentamicin‐loaded fibers and the antibiotic distribution within the fibers were examined by SEM and TEM. The drug delivery profile of the different electrospun fibers was analyzed using a spectrophotometric method. The performance for treating common possible post‐surgical infections was investigated against Staphylococcus epidermis, Pseudomonas aeruginosa and Escherichia coli. The morphology of the electrospun fibers as well as the hydrophilicity of the polymer blends ultimately determined the antibiotic release characteristics. The results indicated that such drug‐loaded fibers can serve as advanced delivery platforms with strong and timing controllable antibacterial properties.

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“…Time indicated is time elapsed after last treatment. gentamicin in human fiberblasts, human myoblasts, hybridoma cells, and HepG2 hepatoma cells (24). It is possible that the toxicity of geneticin may limit its clinical utility.…”

Section: Pharmacokinetic Behavior Of Geneticin In Hemophilia Mouse Plmentioning

confidence: 99%

A mouse model for nonsense mutation bypass therapy shows a dramatic multiday response to geneticin

Yang¹,

Feng²,

Song³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Aminoglycosides can bypass nonsense mutations and are the prototypic agents for translational bypass therapy (TBT). Initial results demonstrate the need for more potent drugs and an in vivo model system for quantitative assessment of TBT. Herein, we present an in vivo system for evaluating the efficacy of premature stop codon management therapies: in vivo quantitative stop codon management repli-sampling TBT efficacy assay (IQSCMaRTEA). Application of IQSCMaRTEA reveals that geneticin is much more efficacious in vivo than gentamicin. Treatment with geneticin elicits a multiday response, and residual F9 antigen can be detected after 3 weeks. These data demonstrate the utility of IQSCMaRTEA for evaluating drugs that bypass nonsense mutations. In addition, IQSCMaRTEA may be helpful for testing inhibitors of nonsensemediated decay, as stop codon management therapy will sometimes require inhibition of nonsense-mediated decay and translational bypass of the nonsense mutation. Furthermore, geneticin, its metabolites, or better tolerated analogues should be evaluated as a general treatment with multiday response for severe genetic disease caused by nonsense mutation.cancer chemotherapy ͉ oncology ͉ nonsense-mediated decay ͉ aminoglycoside ͉ hemophilia A minoglycosides can cause extensive misreading of the mRNA code in vitro (1) and bypass nonsense mutations as demonstrated in Escherichia coli (2), tetrahymena (3), wheat embryo (4), yeast (5), cultured animal cells (6) and human cells (4, 7-9). Barton-Davis et al. (10) described gentamicin-mediated translational bypass therapy (TBT) in the dystrophin gene in a mouse model for muscular dystrophy. Two other mouse models (6, 11) have been described, and clinical trials have been initiated (12,13). The clinical studies have been difficult to perform and disappointing to date, suggesting the need for a better animal model to explore the dose-response relationships of compounds that mediate TBT. No in vivo animal system was heretofore available for direct and quantitative functional assessment of TBT efficacy.We describe such an in vivo system: in vivo quantitative stop codon management repli-sampling TBT efficacy assay (IQSCMaRTEA). Three mutant human minigenes are used as models, two with nonsense mutations with and without dramatic nonsense-mediated decay (NMD) and one with a missense mutation.Hemophilia is the oldest known hereditary bleeding disorder affecting Ϸ1 in 10,000 males. There are Ϸ20,000 hemophilia patients in the United States. Each year, Ϸ400 babies are born with this disease, Ϸ80% with hemophilia A and 20% with hemophilia B (HB). Approximately 70% of hemophilia patients have severe hemophilia, including those with nonsense mutations. TBT has the potential to provide an inexpensive prophylaxis in hemophilia and greatly improve or eliminate symptoms from any severe genetic disease caused by a nonsense mutation (15% of severe inherited genetic disease). However, NMD and sequence context effects complicate the practical application of TBT (14, 15).IQSCMaRTEA allo...

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Cited by 6 publications

References 2 publications

Repairing faulty genes by aminoglycosides: Development of new derivatives of geneticin (G418) with enhanced suppression of diseases-causing nonsense mutations

Repairing faulty genes by aminoglycosides: Development of new derivatives of geneticin (G418) with enhanced suppression of diseases-causing nonsense mutations

Controlled Delivery of Gentamicin Antibiotic from Bioactive Electrospun Polylactide‐Based Ultrathin Fibers

A mouse model for nonsense mutation bypass therapy shows a dramatic multiday response to geneticin

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