Answers are grounded in this paper and cite their sources.
Genome-wide screening shows PIK3CA inhibition improves gene silencing in cancer, indicating a novel strategy for RNA therapeutics.
Lipid nanoparticles (LNPs) are useful carriers for therapeutic siRNA delivery, yet their clinical efficacy remains constrained by insufficient cellular uptake. Here, using a genome‐wide CRISPR knockout screen, multiple genetic modulators of LNP uptake is uncovered, with PIK3CA emerging as a top druggable target. Pharmacologic inhibition of PIK3CA with BAY1082439 – a clinically evaluated small molecule – significantly enhances LNP uptake, siRNA delivery, and gene silencing across diverse epithelial cancer cell lines in vitro. Co‐administration of BAY1082439 with siRNA‐loaded LNPs also better suppressed tumor growth and reduced liver inflammation in vivo, respectively. These findings establish PIK3CA inhibition as a broadly applicable strategy to boost LNP‐mediated RNA interference and highlight the promise of combining functional genomics with nanomaterials to advance RNA‐based therapeutics.
No takes yet. Share an insight, caveat, or question.
Wang et al. (2025) studied this question.
Synapse has enriched 10 related papers. Consider them for comparative context: