α-l-Threose Nucleic Acids as Biocompatible Antisense Oligonucleotides for Suppressing Gene Expression in Living Cells

ACS Applied Materials & Interfaces
Ling Sum LiuPik Kwan Lo

Abstract

Because of the chemical simplicity of α-l-threose nucleic acid (TNA) and its ability to exchange genetic information between itself and RNA, it has attracted significant interest as the RNA ancestor. We herein explore the biological properties and evaluate the potency of sequence-designed TNA polymers to suppress the gene expression in living environments. We found that sequence-specific TNA macromolecules exhibit strong affinity and specificity toward the complementary RNA targets, are highly biocompatible and nontoxic in a living cell system, and readily enter a number of cell lines without using transfecting agents. Particularly, TNA exhibited much stronger enzymatic resistance toward fetal bovine serum or human serum as compared to traditional antisense oligonucleotides, which means that the intrinsic structure of TNA is thoroughly resistant to biological degradation. Importantly, the efficacy of the TNA molecule with green fluorescent protein (GFP) target sequence (anti-GFP TNAs) as antisense agents was first demonstrated in living cells in which these polymers revealed high antisense activity in terms of the degree of inhibition of GFP gene expression. The GFP gene inhibition studies in HeLa and HEK293 cells characterize ...Continue Reading

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Citations

Feb 21, 2019·Small·Yee Ting Elaine ChiuChung Hang Jonathan Choi
Sep 19, 2019·Nucleosides, Nucleotides & Nucleic Acids·Kunihiko Morihiro, Akimitsu Okamoto
Jul 29, 2020·Chemical Communications : Chem Comm·Xuehe LuBaoquan Ding
Apr 15, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hibiki KomineSatoshi Obika
Feb 4, 2021·Accounts of Chemical Research·John C Chaput
Nov 7, 2020·ACS Applied Materials & Interfaces·Ling Sum LiuPik Kwan Lo
May 25, 2021·Journal of the American Chemical Society·Yao WangHanyang Yu
May 18, 2021·Frontiers in Molecular Biosciences·Olga KhorkovaClaes Wahlestedt
Nov 7, 2020·Chemical Communications : Chem Comm·Xintong LiHanyang Yu
Jan 11, 2019·ACS Synthetic Biology·Cailen M McCloskeyJohn C Chaput
Apr 10, 2019·ACS Synthetic Biology·Hershel H LackeyJennifer M Heemstra

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