Downregulation of p21(WAF1/CIP1) and estrogen receptor alpha in MCF-7 cells by antisense oligonucleotides containing locked nucleic acid (LNA)
| Autor: | Anne E. Lykkesfeldt, Henrik M. Pfundheller, Jan Stenvang Jepsen |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
chemistry.chemical_classification
Cyclin-Dependent Kinase Inhibitor p21 Phosphorothioate Oligonucleotides Oligonucleotide Estrogen Receptor alpha Oligonucleotides Estrogen receptor Down-Regulation Cell Cycle Proteins Biology Oligonucleotides Antisense Molecular biology Cell Line chemistry.chemical_compound Biochemistry MCF-7 chemistry Downregulation and upregulation Genetics Molecular Medicine Humans Nucleotide Locked nucleic acid Molecular Biology DNA |
| Zdroj: | Oligonucleotides. 14(2) |
| ISSN: | 1545-4576 |
| Popis: | Locked nucleic acid (LNA) is a nucleic acid analog with very high affinity to complementary RNA and a promising compound in the field of antisense research. The intracellular localization and quantitative uptake of oligonucleotides containing LNA were found to be equivalent to those of phosphorothioate oligonucleotides (PS AONs). The antisense efficiency of LNA-containing oligonucleotides was systematically compared with standard PS AONs targeting expression of two endogenous proteins in the human breast cancer cell line MCF-7, namely, the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and the estrogen receptor alpha (ERalpha). For downregulation of both target proteins, the most efficient design was achieved with oligonucleotides containing LNA monomers in the extremities and a central gap of PS-linked DNA monomers, so called LNA gapmers. Such LNA gapmers caused more potent downregulation of the targeted proteins than PS AONs, whereas fully modified LNA AONs or LNA mixmers (LNA nucleotides interspersed) were inactive. |
| Databáze: | OpenAIRE |
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