Current Development of siRNA Bioconjugates: From Research to the Clinic

Small interfering RNAs (siRNAs) acting via RNA interference mechanisms are able to recognize a homologous mRNA sequence in the cell and induce its degradation. The main problems in the development of siRNA-based drugs for therapeutic use are the low efficiency of siRNA delivery to target cells and t...

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Main Authors: Ivan V. Chernikov, Valentin V. Vlassov, Elena L. Chernolovskaya
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-04-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphar.2019.00444/full
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author Ivan V. Chernikov
Valentin V. Vlassov
Elena L. Chernolovskaya
author_facet Ivan V. Chernikov
Valentin V. Vlassov
Elena L. Chernolovskaya
author_sort Ivan V. Chernikov
collection DOAJ
description Small interfering RNAs (siRNAs) acting via RNA interference mechanisms are able to recognize a homologous mRNA sequence in the cell and induce its degradation. The main problems in the development of siRNA-based drugs for therapeutic use are the low efficiency of siRNA delivery to target cells and the degradation of siRNAs by nucleases in biological fluids. Various approaches have been proposed to solve the problem of siRNA delivery in vivo (e.g., viruses, cationic lipids, polymers, nanoparticles), but all have limitations for therapeutic use. One of the most promising approaches to solve the problem of siRNA delivery to target cells is bioconjugation; i.e., the covalent connection of siRNAs with biogenic molecules (lipophilic molecules, antibodies, aptamers, ligands, peptides, or polymers). Bioconjugates are “ideal nanoparticles” since they do not need a positive charge to form complexes, are less toxic, and are less effectively recognized by components of the immune system because of their small size. This review is focused on strategies and principles for constructing siRNA bioconjugates for in vivo use.
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spelling doaj.art-8c486dde09ce4b9c8b2b8dd5565edf962022-12-21T23:35:34ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-04-011010.3389/fphar.2019.00444452642Current Development of siRNA Bioconjugates: From Research to the ClinicIvan V. ChernikovValentin V. VlassovElena L. ChernolovskayaSmall interfering RNAs (siRNAs) acting via RNA interference mechanisms are able to recognize a homologous mRNA sequence in the cell and induce its degradation. The main problems in the development of siRNA-based drugs for therapeutic use are the low efficiency of siRNA delivery to target cells and the degradation of siRNAs by nucleases in biological fluids. Various approaches have been proposed to solve the problem of siRNA delivery in vivo (e.g., viruses, cationic lipids, polymers, nanoparticles), but all have limitations for therapeutic use. One of the most promising approaches to solve the problem of siRNA delivery to target cells is bioconjugation; i.e., the covalent connection of siRNAs with biogenic molecules (lipophilic molecules, antibodies, aptamers, ligands, peptides, or polymers). Bioconjugates are “ideal nanoparticles” since they do not need a positive charge to form complexes, are less toxic, and are less effectively recognized by components of the immune system because of their small size. This review is focused on strategies and principles for constructing siRNA bioconjugates for in vivo use.https://www.frontiersin.org/article/10.3389/fphar.2019.00444/fullRNAisiRNAbioconjugatechemical modificationspatterns of chemical modifications
spellingShingle Ivan V. Chernikov
Valentin V. Vlassov
Elena L. Chernolovskaya
Current Development of siRNA Bioconjugates: From Research to the Clinic
Frontiers in Pharmacology
RNAi
siRNA
bioconjugate
chemical modifications
patterns of chemical modifications
title Current Development of siRNA Bioconjugates: From Research to the Clinic
title_full Current Development of siRNA Bioconjugates: From Research to the Clinic
title_fullStr Current Development of siRNA Bioconjugates: From Research to the Clinic
title_full_unstemmed Current Development of siRNA Bioconjugates: From Research to the Clinic
title_short Current Development of siRNA Bioconjugates: From Research to the Clinic
title_sort current development of sirna bioconjugates from research to the clinic
topic RNAi
siRNA
bioconjugate
chemical modifications
patterns of chemical modifications
url https://www.frontiersin.org/article/10.3389/fphar.2019.00444/full
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