Systematic chemical modifications of single stranded siRNAs significantly improved CTNNB1 mRNA silencing
| Autor: | Laura Sepp-Lorenzino, Hangchun Zhang, Yi Pei, South Victoria J, Steven L. Colletti, Wonsuk Chang, Daniel Zewge, Matthew G. Stanton, Jillian DiMuzio, Edward C. Sherer, Craig A. Parish, Erin N. Guidry, Walter Strapps |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Small interfering RNA Clinical Biochemistry Trans-acting siRNA Pharmaceutical Science Biochemistry 03 medical and health sciences 0302 clinical medicine RNA interference Drug Discovery Humans Gene silencing Gene Silencing RNA Messenger RNA Small Interfering Molecular Biology beta Catenin Gene knockdown Oligonucleotide Chemistry Organic Chemistry Molecular biology Cell biology RNA silencing HEK293 Cells 030104 developmental biology 030220 oncology & carcinogenesis Nucleic acid Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 26:4513-4517 |
| ISSN: | 0960-894X |
| Popis: | Single-stranded silencing RNAs (ss siRNA), while not as potent as duplex RNAs, have the potential to become a novel platform technology in RNA interference based gene silencing by virtue of their simplicity and plausibly favorable characteristics in pharmacokinetics and biodistribution. Like other therapeutic pharmaceutical agents, ss siRNA can be optimized to achieve higher potency through a structure-activity based approach. Systematic chemical modification at each position of a 21-mer oligonucleotide identified 2',5'-linked 3'-deoxythymidine (3dT) at position 1 and locked nucleic acids (LNAs) at the seed region as key components to afford significant enhancement in knockdown activity both in vitro and in vivo. Further optimization by additional chemical modifications should enable ss siRNA as an alternative gene silencing modality. |
| Databáze: | OpenAIRE |
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