Site-Selective Artificial Ribonucleases: Renaissance of Oligonucleotide Conjugates for Irreversible Cleavage of RNA Sequences
Yaroslav Staroseletz,
Svetlana Gaponova,
Olga Patutina,
Elena Bichenkova,
Bahareh Amirloo,
Thomas Heyman,
Daria Chiglintseva,
Marina Zenkova
Affiliations
Yaroslav Staroseletz
Laboratory of Nucleic Acids Biochemistry, Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev’s Ave. 8, 630090 Novosibirsk, Russia
Svetlana Gaponova
Laboratory of Nucleic Acids Biochemistry, Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev’s Ave. 8, 630090 Novosibirsk, Russia
Olga Patutina
Laboratory of Nucleic Acids Biochemistry, Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev’s Ave. 8, 630090 Novosibirsk, Russia
Elena Bichenkova
School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Rd., Manchester M13 9PT, UK
Bahareh Amirloo
School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Rd., Manchester M13 9PT, UK
Thomas Heyman
School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Rd., Manchester M13 9PT, UK
Daria Chiglintseva
Laboratory of Nucleic Acids Biochemistry, Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev’s Ave. 8, 630090 Novosibirsk, Russia
Marina Zenkova
Laboratory of Nucleic Acids Biochemistry, Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentiev’s Ave. 8, 630090 Novosibirsk, Russia
RNA-targeting therapeutics require highly efficient sequence-specific devices capable of RNA irreversible degradation in vivo. The most developed methods of sequence-specific RNA cleavage, such as siRNA or antisense oligonucleotides (ASO), are currently based on recruitment of either intracellular multi-protein complexes or enzymes, leaving alternative approaches (e.g., ribozymes and DNAzymes) far behind. Recently, site-selective artificial ribonucleases combining the oligonucleotide recognition motifs (or their structural analogues) and catalytically active groups in a single molecular scaffold have been proven to be a great competitor to siRNA and ASO. Using the most efficient catalytic groups, utilising both metal ion-dependent (Cu(II)-2,9-dimethylphenanthroline) and metal ion-free (Tris(2-aminobenzimidazole)) on the one hand and PNA as an RNA recognising oligonucleotide on the other, allowed site-selective artificial RNases to be created with half-lives of 0.5–1 h. Artificial RNases based on the catalytic peptide [(ArgLeu)2Gly]2 were able to take progress a step further by demonstrating an ability to cleave miRNA-21 in tumour cells and provide a significant reduction of tumour growth in mice.
