ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025
KCNN4 as a genomic determinant of cytosolic delivery by the attenuated cationic lytic peptide L17E.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- Protein Modifications for Cellular Protein Delivery.Chemical reviews · 2026Review
- Unveiling the impact of cGMP-dependent protein kinase of Neospora caninum on calcium fluxes and egress functions through quantitative phosphoproteome analysis.Communications biology · 2025Article
- Orchestrating cytosolic access: The partnership of cationic lytic peptide L17E and potassium channel KCa3.1.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
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6 authors.
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Abstract
The development of a cytosolic delivery strategy for biopharmaceuticals is one of the central issues in drug development. Knowledge of the mechanisms underlying these processes may also pave the way for the discovery of novel delivery systems. L17E is an attenuated cationic amphiphilic lytic (ACAL) peptide developed by our research group that shows promise for cytosolic antibody delivery. In this study, given the high efficacy of L17E in cytosolic delivery, we investigated the mechanism of action of L17E in detail. L17E was found to achieve cytosolic delivery predominantly by transient disruption of the plasma membrane without the need for endocytosis. Importantly, the cell-line selectivity studies of L17E revealed a strong correlation between the efficiency of L17E-mediated delivery and the expression level of KCNN4, the gene encoding the calcium-activated potassium channel KCa3.1. Genetic and pharmacological regulation of KCNN4 expression and KCa3.1 activity, respectively, correlate closely with the efficiency of L17E-mediated cytosolic delivery, suggesting the importance of membrane-potential regulation by extracellular Ca
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