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Oligonucleotides conjugated with short chemically defined polyethylene glycol chains are efficient antisense agents.

Shokrzadeh N, Winkler AM, Dirin M, Winkler J - Bioorg. Med. Chem. Lett. (2014)

Bottom Line: We examined the use of short PEG ligands on the in vitro effect of antisense agents.Circular dichroism showed that the tethering of PEG12-chains to phosphodiester and phosphorothioate oligonucleotides had no influence on their secondary structure and did not reduce the affinity to the counter strand.In an in vitro tumor model, a luciferase reporter assay indicated unchanged gene silencing activity compared to unmodified compounds, and even slightly superior target down regulation was found after treatment with a phosphorothioate modified conjugate.

View Article: PubMed Central - PubMed

Affiliation: University of Vienna, Department of Pharmaceutical Chemistry, Althanstraße 14, 1090 Vienna, Austria.

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Effect of PEGylated phosphorothioate antisense oligonucleotides on cell proliferation. To evaluate unspecific toxicity, cell proliferation rates were assayed after treatment with antisense oligonucleotides. The indicated compounds were applied without transfection reagents, and proliferation was evaluated after a 24 h incubation period with an MTS assay.18 No significant influence on proliferation was detected for any compound, indicating no apparent toxic effects caused by the PEG conjugations (n = 3, error bars are SEM).
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f0015: Effect of PEGylated phosphorothioate antisense oligonucleotides on cell proliferation. To evaluate unspecific toxicity, cell proliferation rates were assayed after treatment with antisense oligonucleotides. The indicated compounds were applied without transfection reagents, and proliferation was evaluated after a 24 h incubation period with an MTS assay.18 No significant influence on proliferation was detected for any compound, indicating no apparent toxic effects caused by the PEG conjugations (n = 3, error bars are SEM).

Mentions: To exclude any unspecific or toxic effects, cell proliferation rates were assessed after treatment with the modified oligonucleotides, applied without transfection enhancer (Fig. 3). In concentrations that resulted in successful gene silencing, none of the oligonucleotides reduced proliferation by more than 15%, with a 13% reduction caused by non-PEGylated phosphorothioate 7 (100 nM) being the most pronounced effect. Thus, PEGylation did not induce any negative effect on proliferation, indicating a good in vitro safety profile of the conjugates.


Oligonucleotides conjugated with short chemically defined polyethylene glycol chains are efficient antisense agents.

Shokrzadeh N, Winkler AM, Dirin M, Winkler J - Bioorg. Med. Chem. Lett. (2014)

Effect of PEGylated phosphorothioate antisense oligonucleotides on cell proliferation. To evaluate unspecific toxicity, cell proliferation rates were assayed after treatment with antisense oligonucleotides. The indicated compounds were applied without transfection reagents, and proliferation was evaluated after a 24 h incubation period with an MTS assay.18 No significant influence on proliferation was detected for any compound, indicating no apparent toxic effects caused by the PEG conjugations (n = 3, error bars are SEM).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4263527&req=5

f0015: Effect of PEGylated phosphorothioate antisense oligonucleotides on cell proliferation. To evaluate unspecific toxicity, cell proliferation rates were assayed after treatment with antisense oligonucleotides. The indicated compounds were applied without transfection reagents, and proliferation was evaluated after a 24 h incubation period with an MTS assay.18 No significant influence on proliferation was detected for any compound, indicating no apparent toxic effects caused by the PEG conjugations (n = 3, error bars are SEM).
Mentions: To exclude any unspecific or toxic effects, cell proliferation rates were assessed after treatment with the modified oligonucleotides, applied without transfection enhancer (Fig. 3). In concentrations that resulted in successful gene silencing, none of the oligonucleotides reduced proliferation by more than 15%, with a 13% reduction caused by non-PEGylated phosphorothioate 7 (100 nM) being the most pronounced effect. Thus, PEGylation did not induce any negative effect on proliferation, indicating a good in vitro safety profile of the conjugates.

Bottom Line: We examined the use of short PEG ligands on the in vitro effect of antisense agents.Circular dichroism showed that the tethering of PEG12-chains to phosphodiester and phosphorothioate oligonucleotides had no influence on their secondary structure and did not reduce the affinity to the counter strand.In an in vitro tumor model, a luciferase reporter assay indicated unchanged gene silencing activity compared to unmodified compounds, and even slightly superior target down regulation was found after treatment with a phosphorothioate modified conjugate.

View Article: PubMed Central - PubMed

Affiliation: University of Vienna, Department of Pharmaceutical Chemistry, Althanstraße 14, 1090 Vienna, Austria.

Show MeSH
Related in: MedlinePlus