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<front>
<journal-meta>
<journal-id journal-id-type="doi">10.1002/(ISSN)1521-3773</journal-id>
<journal-id journal-id-type="publisher-id">ANIE</journal-id>
<journal-title-group>
<journal-title xml:lang="en">Angewandte Chemie International Edition</journal-title>
<abbrev-journal-title abbrev-type="publisher" xml:lang="en">Angew. Chem. Int. Ed.</abbrev-journal-title>
</journal-title-group>
<issn publication-format="ppub">1433-7851</issn>
<issn publication-format="epub">1521-3773</issn>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.1002/anie.202412925</article-id>
<article-id pub-id-type="publisher-id">ANIE202412925</article-id>
<article-categories>
<subj-group subj-group-type="overline" xml:lang="en">
<subject>Minireview</subject>
</subj-group>
<subj-group subj-group-type="heading" xml:lang="en">
<subject>Minireview</subject>
<subj-group subj-group-type="heading" xml:lang="en">
<subject>RNA Degraders</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title xml:lang="en">Small Molecule RNA Degraders</article-title>
</title-group>
<contrib-group>
<contrib id="anie202412925-cr-0001" contrib-type="author" corresp="yes">
<name>
<surname>Bonet‐Aleta</surname>
<given-names>Javier</given-names>
<prefix>Dr.</prefix>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1791-0188</contrib-id>
<email>gb453@cam.ac.uk</email>
<xref ref-type="aff" rid="anie202412925-aff-0001">
<sup>1</sup>
</xref>
</contrib>
<contrib id="anie202412925-cr-0002" contrib-type="author">
<name>
<surname>Maehara</surname>
<given-names>Tomoaki</given-names>
<prefix>Dr.</prefix>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0009-0002-6219-320X</contrib-id>
<xref ref-type="aff" rid="anie202412925-aff-0001">
<sup>1</sup>
</xref>
</contrib>
<contrib id="anie202412925-cr-0003" contrib-type="author">
<name>
<surname>Craig</surname>
<given-names>Benjamin A.</given-names>
</name>
<xref ref-type="aff" rid="anie202412925-aff-0001">
<sup>1</sup>
</xref>
</contrib>
<contrib id="anie202412925-cr-0004" contrib-type="author" corresp="yes">
<name>
<surname>Bernardes</surname>
<given-names>Gonçalo J. L.</given-names>
<prefix>Prof.</prefix>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6594-8917</contrib-id>
<email>jb2648@cam.ac.uk</email>
<xref ref-type="aff" rid="anie202412925-aff-0001">
<sup>1</sup>
</xref>
</contrib>
</contrib-group>
<aff id="anie202412925-aff-0001">
<label>
<sup>1</sup>
</label>

<named-content content-type="organisation-division">Yusuf Hamied Department of Chemistry</named-content>

<institution>University of Cambridge</institution>

<postal-code>CB2 1EW</postal-code>
 <city>Cambridge</city>
 <country country="GB">United Kingdom</country>

</aff>
<pub-date date-type="pub" publication-format="electronic"><day>17</day>
<month>10</month>
<year>2024</year>
</pub-date><elocation-id>e202412925</elocation-id>
<history>

<date date-type="received">
<day>09</day>
<month>07</month>
<year>2024</year>
</date>

</history>
<permissions>
<copyright-statement content-type="issue-copyright">© 2024 Wiley-VCH GmbH</copyright-statement>
<copyright-statement content-type="article-copyright">© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH</copyright-statement>
<copyright-year>2024</copyright-year>
<copyright-holder>© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH</copyright-holder>
<license>
<ali:license_ref>http://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open access article under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution</ext-link> License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract xml:lang="en" abstract-type="main">
<title>Abstract</title>
<p xml:lang="en">RNA is a central molecule in life, involved in a plethora of biological processes and playing a key role in many diseases. Targeting RNA emerges as a significant endeavor in drug discovery, diverging from conventional protein‐centric approaches to tackle various pathologies. Whilst identifying small molecules that bind to specific RNA regions is the first step, the abundance of non‐functional RNA segments renders many interactions biologically inert. Consequently, small molecule binding does not necessarily meet stringent criteria for clinical translation, calling for solutions to push the field forward. Converting RNA‐binders into RNA‐degraders presents a promising avenue to enhance RNA‐targeting. This mini‐review outlines strategies and exemplars wherein simple small molecule RNA binders are reprogrammed into active degraders through the linkage of functional groups. These approaches encompass mechanisms that induce degradation via endogenous enzymes, termed RIBOTACs, as well as those with functional moieties acting autonomously to degrade RNA. Through this exploration, we aim to offer insights into advancing RNA‐targeted therapeutic strategies.</p>
</abstract>
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<kwd id="anie202412925-kwd-0001">RNA</kwd>
<kwd id="anie202412925-kwd-0002">small-molecule</kwd>
<kwd id="anie202412925-kwd-0003">degradation</kwd>
<kwd id="anie202412925-kwd-0004">proximity-induced</kwd>
<kwd id="anie202412925-kwd-0005">therapy</kwd>
</kwd-group>
<counts>
<fig-count count="9"/>
<table-count count="0"/>
<ref-count count="126"/>
<page-count count="12"/>
<word-count count="0"/>
</counts>
</article-meta>
</front>
</article>