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Genes 2018, 9(2), 74; https://doi.org/10.3390/genes9020074

Covalent Strategies for Targeting Messenger and Non-Coding RNAs: An Updated Review on siRNA, miRNA and antimiR Conjugates

1
Institute of Advanced Chemistry of Catalonia (IQAC, CSIC), Jordi Girona 18-26, 08034 Barcelona, Spain
2
Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Jordi Girona 18-26, 08034 Barcelona, Spain
3
Coimbra Chemistry Centre, (CQC), Department of Chemistry, University of Coimbra, Rua Larga, 3004-535 Coimbra, Portugal
*
Authors to whom correspondence should be addressed.
Received: 4 January 2018 / Revised: 26 January 2018 / Accepted: 26 January 2018 / Published: 6 February 2018
(This article belongs to the Special Issue Non-coding RNAs)
Full-Text   |   PDF [3931 KB, uploaded 6 February 2018]   |  

Abstract

Oligonucleotide-based therapy has become an alternative to classical approaches in the search of novel therapeutics involving gene-related diseases. Several mechanisms have been described in which demonstrate the pivotal role of oligonucleotide for modulating gene expression. Antisense oligonucleotides (ASOs) and more recently siRNAs and miRNAs have made important contributions either in reducing aberrant protein levels by sequence-specific targeting messenger RNAs (mRNAs) or restoring the anomalous levels of non-coding RNAs (ncRNAs) that are involved in a good number of diseases including cancer. In addition to formulation approaches which have contributed to accelerate the presence of ASOs, siRNAs and miRNAs in clinical trials; the covalent linkage between non-viral vectors and nucleic acids has also added value and opened new perspectives to the development of promising nucleic acid-based therapeutics. This review article is mainly focused on the strategies carried out for covalently modifying siRNA and miRNA molecules. Examples involving cell-penetrating peptides (CPPs), carbohydrates, polymers, lipids and aptamers are discussed for the synthesis of siRNA conjugates whereas in the case of miRNA-based drugs, this review article makes special emphasis in using antagomiRs, locked nucleic acids (LNAs), peptide nucleic acids (PNAs) as well as nanoparticles. The biomedical applications of siRNA and miRNA conjugates are also discussed. View Full-Text
Keywords: covalent approach; gene delivery; gene therapy; non-coding RNA; miRNA technology; nucleic acid conjugates; RNA interference covalent approach; gene delivery; gene therapy; non-coding RNA; miRNA technology; nucleic acid conjugates; RNA interference
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Grijalvo, S.; Alagia, A.; Jorge, A.F.; Eritja, R. Covalent Strategies for Targeting Messenger and Non-Coding RNAs: An Updated Review on siRNA, miRNA and antimiR Conjugates. Genes 2018, 9, 74.

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