Proximity-Induced Nucleic Acid Degrader (PINAD) Approach to Targeted RNA Degradation Using Small Molecules.

ABSTRACT: Nature has evolved intricate machinery to target and degrade RNA, and some of these molecular mechanisms can be adapted for therapeutic use. Small interfering RNAs and RNase H-inducing oligonucleotides have yielded therapeutic agents against diseases that cannot be tackled using protein-centered approaches. Because these therapeutic agents are nucleic acid-based, they have several inherent drawbacks which include poor cellular uptake and stability. Here we report a new approach to target and degrade RNA using small molecules, proximity-induced nucleic acid degrader (PINAD). We have utilized this strategy to design two families of RNA degraders which target two different RNA structures within the genome of SARS-CoV-2: G-quadruplexes and the betacoronaviral pseudoknot. We demonstrate that th

SUBMITTER: Mikutis S 

PROVIDER: S-EPMC10214512 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature