Targeted protein degradation with proteolysis-targeting chimeras (PROTACs) has the potential to tackle disease-causing proteins that have historically been highly challenging to target with conventional small molecules. This article summarizes the first two decades of PROTAC discovery and discusses key areas for the future of this therapeutic modality, including establishing the target classes for which it is most suitable and extending its application beyond oncology.

Studying RNA dynamics in vivo often relies on fluorogenic approaches, but these can be hampered by factors such as limited sensitivity and sample autofluorescence. Here, the authors describe an ultrasensitive platform for RNA imaging, which features RNA tags that recruit light-emitting luciferase fragments.

AZD0156, an ATM kinase inhibitor in clinical development, shows promising multistage antiplasmodial activity by targeting Plasmodium falciparum phosphatidylinositol 4-kinase (PfPI4Kβ). With an improv...

Natural alcohol and sugar dehydrogenases that utilize the redox cofactor pyrroloquinoline quinone (PQQ) can be repurposed for enantioselective photoredox catalysis. Upon blue-light irradiation, redox...

Computational biology and bioinformatics provide vast data gold-mines from protein sequences, ideal for Language Models (LMs) taken from Natural Language Processing (NLP). These LMs reach for new pred...

Song et al. developed a programmable RNA base editor, termed RESTART, relying on guide snoRNA to mediate site-specific pseudouridylation in mammalian cells. RESTART was applied to nonsense mutations i...

The medicinal plant Catharanthus roseus is a source of leading anticancer drugs. The monoterpene indole alkaloid (MIA) biosynthetic pathway in C. roseus has now been analyzed using a complementary, multi-omics, single-cell approach. This identified clusters of genes involved in MIA biosynthesis and cell-type-specific partitioning in the MIA biosynthetic pathway.