Affiliation:
1. MOE Key Laboratory of Spectrochemical Analysis and Instrumentation State Key Laboratory of Physical Chemistry of Solid Surfaces Key Laboratory for Chemical Biology of Fujian Province Department of Chemical Biology College of Chemistry and Chemical Engineering Xiamen University Xiamen 361000 China
2. Innovation Laboratory for Sciences Technologies of Energy Materials of Fujian Province Xiamen 361000 China
Abstract
AbstractMicroRNA (miRNA) molecules play crucial roles in a variety of diseases, making miRNA targeting a burgeoning field in medicinal chemistry. Ribonuclease targeting chimeras (RIBOTACs) present a compelling approach for RNA degradation. However, small molecule‐based RIBOTAC requires an expensive and time‐consuming screening process, and is difficult to directly target miRNA due to its short length lacking secondary structure. Antisense oligonucleotide (ASO)‐based RIBOTAC is easy to design but with poor cell permeability. While both of them lack the specificity for tumor targeting. In this study, the first Aptamer‐RIBOTAC (ARIBOTAC) chimera is designed based on ASO to achieve precise degradation of miRNA in a tumor cell‐specific manner for precise cancer therapy. This chimera exhibits a remarkable ability to specifically identify and enter cancer cells, trigger localized activation of endogenous RNase L, and selectively cleave miRNAs that are complementary to ASO. The efficacy and universality of the ARIBOTAC strategy both in vitro and in vivo by degrading oncogenic miR‐210‐3p and miR‐155‐5p are validated. These findings underscore the potential of the ARIBOTAC strategy as a promising avenue for cancer therapy by precisely targeting cancer‐associated miRNAs.
Funder
National Fund for Fostering Talents of Basic Science
Fundamental Research Funds for the Central Universities
National Natural Science Foundation of China
Key Technologies Research and Development Program
Cited by
1 articles.
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