New opportunities for designing effective small interfering RNAs

0520583 - BC 2020 RIV GB eng J - Journal Article
Valdés, James J. - Miller, A. D.
New opportunities for designing effective small interfering RNAs.
Scientific Reports. Roč. 9, NOV 6 2019 (2019), č. článku 16146. ISSN 2045-2322. E-ISSN 2045-2322
Institutional support: RVO:60077344
Keywords : active-site * hepatitis-c * all-atom * protein * replication * exploration * inhibition * pseudoknot * expression * pele
OECD category: Microbiology
Impact factor: 3.998, year: 2019
Method of publishing: Open access
https://www.nature.com/articles/s41598-019-52303-5.pdf

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.
Permanent Link: http://hdl.handle.net/11104/0305239