α-l-Threose Nucleic Acids as Biocompatible Antisense Oligonucleotides for Suppressing Gene Expression in Living Cells
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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Selection of threose nucleic acid aptamers to block PD-1/PD-L1 interaction for cancer immunotherapy.
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