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Chemical Modifications in Nucleic Acids for Therapeutic and Diagnostic Applications
Chem Rec. 2022 Apr;22(4):e202100270. doi: 10.1002/tcr.202100270. Epub 2021 Dec 8.ABSTRACTThe last decade has witnessed the blooming of nucleic acids for therapeutic and diagnostic applications. In the present article, we describe the most important results from our group in this area covering the international context that surrounded this research. These include the study of modifications at the terminal and internal positions of siRNA duplexes to enhance nuclease resistance, increase loading of the antisense strand to RISC and avoid side effects such as activation of immune response and sense strand misloading. Then, we d...
Source: Chemical Record - April 7, 2022 Category: Chemistry Authors: Carme F àbrega Anna Avi ñó Ramon Eritja Source Type: research

Cell-selective siRNA delivery using glycosylated dynamic covalent polymers self-assembled in situ by RNA-templating.
Abstract Dynamic covalent libraries enable exploring complex chemical systems from which bioactive assemblies can adaptively emerge through template effects. In this work, we studied dynamic covalent libraries made of complementary bifunctional cationic peptides, yielding a diversity of species from macrocycles to polymers. Although polymers are typically expressed only at high concentration, we found that siRNA act as a template in the formation of dynamic covalent polymers at low concentration in a process guided by electrostatic binding. Using a glycosylated building block, we were able to show that this templa...
Source: Angewandte Chemie - December 8, 2020 Category: Chemistry Authors: Laroui N, Coste M, Su D, Ali L, Bessin Y, Barboiu M, Gary-Bobo M, Bettache N, Ulrich S Tags: Angew Chem Int Ed Engl Source Type: research

Synthesis, RNAi activity and nuclease-resistant properties of apolar carbohydrates siRNA conjugates.
Abstract Oligoribonucleotide conjugates carrying apolar carbohydrates at the 5'-end and the corresponding siRNA duplexes have been prepared using phosphoramidite chemistry. All the carbohydrate-siRNA derivatives were compatible with RNA interference machinery if transfected with oligofectamine. In the absence of a transfection agent, some of them exerted certain reduction of gene expression. Double-tailed permethylated glucose conjugated to siRNA through a long spacer inhibited gene expression up to 26% compared to the scrambled duplex. Such modifications contribute positively to the stability of oligoribonucleoti...
Source: Bioorganic and Medicinal Chemistry Letters - May 28, 2013 Category: Chemistry Authors: Vengut-Climent E, Terrazas M, Lucas R, Arévalo-Ruiz M, Eritja R, Morales JC Tags: Bioorg Med Chem Lett Source Type: research