Publication
Proximity-Induced Nucleic Acid Degrader (PINAD) approach to targeted RNA degradation using small molecules
| dc.contributor.author | Mikutis, Sigitas | |
| dc.contributor.author | Rebelo, Maria | |
| dc.contributor.author | Yankova, Eliza | |
| dc.contributor.author | Gu, Muxin | |
| dc.contributor.author | Tang, Cong | |
| dc.contributor.author | Coelho, Ana R. | |
| dc.contributor.author | Yang, Mo | |
| dc.contributor.author | Hazemi, Madoka E. | |
| dc.contributor.author | Pires de Miranda, Marta | |
| dc.contributor.author | Eleftheriou, Maria | |
| dc.contributor.author | Robertson, Max | |
| dc.contributor.author | Vassiliou, George S. | |
| dc.contributor.author | Adams, David J. | |
| dc.contributor.author | Simas, J. Pedro | |
| dc.contributor.author | Corzana, Francisco | |
| dc.contributor.author | Schneekloth, John S. | |
| dc.contributor.author | Tzelepis, Konstantinos | |
| dc.contributor.author | Bernardes, Gonçalo J.L. | |
| dc.date.accessioned | 2023-05-17T08:17:27Z | |
| dc.date.available | 2023-05-17T08:17:27Z | |
| dc.date.issued | 2023-05-24 | |
| dc.description.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 these novel molecules degrade their targets using in vitro, in cellulo, and in vivo SARS-CoV-2 infection models. Our strategy allows any RNA binding small molecule to be converted into a degrader, empowering RNA binders that are not potent enough to exert a phenotypic effect on their own. PINAD raises the possibility of targeting and destroying any disease-related RNA species, which can greatly expand the space of druggable targets and diseases. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.doi | 10.1021/acscentsci.3c00015 | pt_PT |
| dc.identifier.eid | 85156240026 | |
| dc.identifier.issn | 2374-7943 | |
| dc.identifier.pmc | PMC10214512 | |
| dc.identifier.pmid | 37252343 | |
| dc.identifier.uri | http://hdl.handle.net/10400.14/41145 | |
| dc.identifier.wos | 000981755900001 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt_PT |
| dc.title | Proximity-Induced Nucleic Acid Degrader (PINAD) approach to targeted RNA degradation using small molecules | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 904 | |
| oaire.citation.issue | 5 | |
| oaire.citation.startPage | 892 | |
| oaire.citation.title | ACS Central Science | pt_PT |
| oaire.citation.volume | 9 | |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |