TY  - JOUR
AU  - Genz, Luca
AU  - Nair, Sanjana
AU  - Sweeney, Aaron
AU  - Topf, Maya
TI  - Drug targeting of protein-nucleic acid interactions
JO  - Current opinion in structural biology
VL  - 95
SN  - 0959-440X
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - PUBDB-2025-04336
SP  - 103165 
PY  - 2025
N1  - and DFG CRC1648
AB  - Protein–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. 
LB  - PUB:(DE-HGF)16
DO  - DOI:10.1016/j.sbi.2025.103165
UR  - https://bib-pubdb1.desy.de/record/639214
ER  -