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Modulating NLRP3 splicing with antisense oligonucleotides to control pathological inflammation.


ABSTRACT: Inflammation has an essential role in healing. However, over-active inflammation disrupts normal cellular functions and can be life-threatening when not resolved. The NLR family pyrin domain-containing 3 (NLRP3) inflammasome, a component of the innate immune system, is an intracellular multiprotein complex that senses stress-associated signals, and, for this reason is a promising therapeutic target for treating unresolved, pathogenic inflammation. Alternative splicing of NLRP3 RNA has been suggested as a regulatory mechanism for inflammasome activation, as some spliced isoforms encode NLRP3 proteins with compromised function. Here, we take advantage of this natural regulatory mechanism and devise a way to control pathogenic inflammation using splice-switching antisense oligonucleotides (AS

SUBMITTER: Klein R 

PROVIDER: S-EPMC12596483 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature