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New opportunities for designing effective small interfering RNAs
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SYSNO ASEP 0520583 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název New opportunities for designing effective small interfering RNAs Tvůrce(i) Valdés, James J. (BC-A) RID, ORCID
Miller, A. D. (GB)Celkový počet autorů 2 Číslo článku 16146 Zdroj.dok. Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322
Roč. 9, NOV 6 2019 (2019)Poč.str. 10 s. Forma vydání Online - E Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova active-site ; hepatitis-c ; all-atom ; protein ; replication ; exploration ; inhibition ; pseudoknot ; expression ; pele Vědní obor RIV EE - Mikrobiologie, virologie Obor OECD Microbiology Způsob publikování Open access Institucionální podpora BC-A - RVO:60077344 UT WOS 000494636800001 EID SCOPUS 85074716808 DOI 10.1038/s41598-019-52303-5 Anotace Small interfering RNAs (siRNAs) that silence genes of infectious diseases are potentially potent drugs. A continuing obstacle for siRNA-based drugs is how to improve their efficacy for adequate dosage. To overcome this obstacle, the interactions of antiviral siRNAs, tested in vivo, were computationally examined within the RNA-induced silencing complex (RISC). Thermodynamics data show that a persistent RISC cofactor is significantly more exothermic for effective antiviral siRNAs than their ineffective counterparts. Detailed inspection of viral RNA secondary structures reveals that effective antiviral siRNAs target hairpin or pseudoknot loops. These structures are critical for initial RISC interactions since they partially lack intramolecular complementary base pairing. Importing two temporary RISC cofactors from magnesium-rich hairpins and/or pseudoknots then kickstarts full RNA hybridization and hydrolysis. Current siRNA design guidelines are based on RNA primary sequence data. Herein, the thermodynamics of RISC cofactors and targeting magnesium-rich RNA secondary structures provide additional guidelines for improving siRNA design. Pracoviště Biologické centrum (od r. 2006) Kontakt Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Rok sběru 2020 Elektronická adresa https://www.nature.com/articles/s41598-019-52303-5.pdf
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