Multivalent DNAzyme agents for cleaving folded RNA.

Autor:	Dubovichenko MV; Laboratory of Frontier Nucleic Acid Technologies in Gene Therapy of Cancer, SCAMT Institute, ITMO University, Saint-Petersburg, 191002, Russia., Batsa M; Laboratory of Frontier Nucleic Acid Technologies in Gene Therapy of Cancer, SCAMT Institute, ITMO University, Saint-Petersburg, 191002, Russia., Bobkov GA; Laboratory of Frontier Nucleic Acid Technologies in Gene Therapy of Cancer, SCAMT Institute, ITMO University, Saint-Petersburg, 191002, Russia., Vlasov GS; Laboratory of Frontier Nucleic Acid Technologies in Gene Therapy of Cancer, SCAMT Institute, ITMO University, Saint-Petersburg, 191002, Russia., El-Deeb AA; Laboratory of Frontier Nucleic Acid Technologies in Gene Therapy of Cancer, SCAMT Institute, ITMO University, Saint-Petersburg, 191002, Russia., Kolpashchikov DM; Laboratory of Frontier Nucleic Acid Technologies in Gene Therapy of Cancer, SCAMT Institute, ITMO University, Saint-Petersburg, 191002, Russia.; Chemistry Department, University of Central Florida, Orlando, FL 32816, USA.; Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32816, USA.; National Center for Forensic Science, University of Central Florida, Orlando, FL, 32816, USA.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2024 Jun 10; Vol. 52 (10), pp. 5866-5879.
DOI:	10.1093/nar/gkae295
Abstrakt:	Multivalent recognition and binding of biological molecules is a natural phenomenon that increases the binding stability (avidity) without decreasing the recognition specificity. In this study, we took advantage of this phenomenon to increase the efficiency and maintain high specificity of RNA cleavage by DNAzymes (Dz). We designed a series of DNA constructs containing two Dz agents, named here bivalent Dz devices (BDD). One BDD increased the cleavage efficiency of a folded RNA fragment up to 17-fold in comparison with the Dz of a conventional design. Such an increase was achieved due to both the improved RNA binding and the increased probability of RNA cleavage by the two catalytic cores. By moderating the degree of Dz agent association in BDD, we achieved excellent selectivity in differentiating single-base mismatched RNA, while maintaining relatively high cleavage rates. Furthermore, a trivalent Dz demonstrated an even greater efficiency than the BDD in cleaving folded RNA. The data suggests that the cooperative action of several RNA-cleaving units can significantly improve the efficiency and maintain high specificity of RNA cleavage, which is important for the development of Dz-based gene knockdown agents. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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