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Peptide nucleic acids are synthetic polymers that mimic the structure of DNA or RNA. PNAs are used in various molecular biology techniques involving specific recognition of a complementary DNA or RNA strand and have been investigated as the basis for diagnostics and antisense therapies.
Off-target toxicity of antisense oligonucleotides (ASOs) poses a challenge for their clinical use. Here, authors develop a toehold-bearing ASO architecture that mitigates a broad spectrum of off-target interactions, significantly enhancing the safety profile of ASO drugs.
Otoupal et al. use a systematic approach to investigate the effects of fitness neutral gene perturbations and antibiotic synergy in Escherichia coli. These neutral fitness interactions worked as co-therapies in a Salmonella enterica infection and informed the design of re-sensitization therapies in multi-drug resistant E. coli and Klebisiella pneumoniae clinical isolates.
The authors show the endocytotic adaptor subunit called AP2A2 is differentially expressed in CGRP+ nociceptors. Locally inhibiting nociceptor endocytosis with a lipidated AP2 inhibitor peptide reduces acute and chronic pain-like behaviour in mice and rats, indicating prolonged analgesia.
Epstein-Barr virus (EBV) tegument proteins BBRF2 and BSRF1 have been suggested to form a hetero-complex. Here, He et al. provide the crystal structures of BBRF2 alone and in complex with BSRF1 and suggest that the complex tethers EBV nucleocapsids to the Golgi membrane, facilitating secondary envelopment.
Findeisen et al. have engineered IC7Fc, a cytokine for the treatment of type 2 diabetes, that selectively activates beneficial metabolic pathways systemically and in metabolic tissues without promoting an inflammatory response.
A process in which peptide nucleic acids may be used for in vitro evolution has been developed. This method can offer enormous opportunities to evolve stable, non-natural molecules for therapeutic applications.
