000639214 001__ 639214 000639214 005__ 20251014215458.0 000639214 0247_ $$2doi$$a10.1016/j.sbi.2025.103165 000639214 0247_ $$2ISSN$$a0959-440X 000639214 0247_ $$2ISSN$$a1879-033X 000639214 0247_ $$2datacite_doi$$a10.3204/PUBDB-2025-04336 000639214 037__ $$aPUBDB-2025-04336 000639214 041__ $$aEnglish 000639214 082__ $$a570 000639214 1001_ $$0P:(DE-H253)PIP1097784$$aGenz, Luca$$b0 000639214 245__ $$aDrug targeting of protein-nucleic acid interactions 000639214 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2025 000639214 3367_ $$2DRIVER$$aarticle 000639214 3367_ $$2DataCite$$aOutput Types/Journal article 000639214 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1760447374_2867353 000639214 3367_ $$2BibTeX$$aARTICLE 000639214 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000639214 3367_ $$00$$2EndNote$$aJournal Article 000639214 500__ $$aand DFG CRC1648 000639214 520__ $$aProtein–nucleic acid interactions are vital to gene regulation and disease, yet have long been considered “undruggable.” Recent advances are reshaping this paradigm, enabling therapeutic targeting of DNA- and RNA-binding proteins. In this review, we highlight four major strategies: (1) direct disruption of protein-nucleic acid binding, (2) stabilization of specific complexes or conformations, (3) targeted degradation of interaction partners, and (4) allosteric modulation. We explore key examples across transcription factors, RNA-binding proteins, and DNA repair proteins, and emphasize emerging chemical, structural, and computational techniques that are accelerating discovery. Together, by intervening directly in the gene regulatory machinery, these approaches expand the druggable genome and open new avenues for treating cancer, genetic disorders, and viral infections. 000639214 536__ $$0G:(DE-HGF)POF4-899$$a899 - ohne Topic (POF4-899)$$cPOF4-899$$fPOF IV$$x0 000639214 588__ $$aDataset connected to CrossRef, Journals: bib-pubdb1.desy.de 000639214 693__ $$0EXP:(DE-MLZ)NOSPEC-20140101$$5EXP:(DE-MLZ)NOSPEC-20140101$$eNo specific instrument$$x0 000639214 7001_ $$0P:(DE-H253)PIP1101921$$aNair, Sanjana$$b1 000639214 7001_ $$0P:(DE-H253)PIP1100083$$aSweeney, Aaron$$b2 000639214 7001_ $$0P:(DE-H253)PIP1094132$$aTopf, Maya$$b3$$eCorresponding author 000639214 773__ $$0PERI:(DE-600)2019233-2$$a10.1016/j.sbi.2025.103165$$gVol. 95, p. 103165 -$$p103165 $$tCurrent opinion in structural biology$$v95$$x0959-440X$$y2025 000639214 8564_ $$uhttps://bib-pubdb1.desy.de/record/639214/files/1-s2.0-S0959440X25001836-main.pdf$$yOpenAccess 000639214 8564_ $$uhttps://bib-pubdb1.desy.de/record/639214/files/1-s2.0-S0959440X25001836-main.pdf?subformat=pdfa$$xpdfa$$yOpenAccess 000639214 909CO $$ooai:bib-pubdb1.desy.de:639214$$popenaire$$popen_access$$pVDB$$pdriver$$pdnbdelivery 000639214 9101_ $$0I:(DE-H253)_CSSB-20140311$$6P:(DE-H253)PIP1097784$$aCentre for Structural Systems Biology$$b0$$kCSSB 000639214 9101_ $$0I:(DE-HGF)0$$6P:(DE-H253)PIP1097784$$aExternal Institute$$b0$$kExtern 000639214 9101_ $$0I:(DE-H253)_CSSB-20140311$$6P:(DE-H253)PIP1101921$$aCentre for Structural Systems Biology$$b1$$kCSSB 000639214 9101_ $$0I:(DE-H253)_CSSB-20140311$$6P:(DE-H253)PIP1100083$$aCentre for Structural Systems Biology$$b2$$kCSSB 000639214 9101_ $$0I:(DE-H253)_CSSB-20140311$$6P:(DE-H253)PIP1094132$$aCentre for Structural Systems Biology$$b3$$kCSSB 000639214 9101_ $$0I:(DE-HGF)0$$6P:(DE-H253)PIP1094132$$aExternal Institute$$b3$$kExtern 000639214 9131_ $$0G:(DE-HGF)POF4-899$$1G:(DE-HGF)POF4-890$$2G:(DE-HGF)POF4-800$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bProgrammungebundene Forschung$$lohne Programm$$vohne Topic$$x0 000639214 9141_ $$y2025 000639214 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2024-12-09 000639214 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2024-12-09 000639214 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2024-12-09 000639214 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0 000639214 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2024-12-09 000639214 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bCURR OPIN STRUC BIOL : 2022$$d2024-12-09 000639214 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2024-12-09 000639214 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2024-12-09 000639214 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2024-12-09 000639214 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 000639214 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2024-12-09 000639214 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bCURR OPIN STRUC BIOL : 2022$$d2024-12-09 000639214 915__ $$0StatID:(DE-HGF)1120$$2StatID$$aDBCoverage$$bBIOSIS Reviews Reports And Meetings$$d2024-12-09 000639214 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2024-12-09 000639214 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz$$d2024-12-09$$wger 000639214 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2024-12-09 000639214 9201_ $$0I:(DE-H253)CSSB-LIV_UKE-MT-20220525$$kCSSB-LIV/UKE-MT$$lCSSB - Leibniz-Institut für Experimentelle Virologie (LIV) / UKE - Maya Topf$$x0 000639214 980__ $$ajournal 000639214 980__ $$aVDB 000639214 980__ $$aUNRESTRICTED 000639214 980__ $$aI:(DE-H253)CSSB-LIV_UKE-MT-20220525 000639214 9801_ $$aFullTexts