Document Type

Response or Comment

Publication Date

1-21-2025

Abstract

In this issue of Molecular Therapy, the study by Kuriyama et al.1 represents an advance in the field of intracellular delivery systems by elucidating a novel mechanism for cytosolic delivery mediated by a cationic amphiphilic lytic peptide L17E (IWLTALKFLGKHAAKHEAKQQLSKL-amide). The investigators demonstrate that the peptide achieves cytosolic delivery primarily through transient plasma membrane disruption, bypassing some of the endocytic pathways, and highlight the pivotal role of the calcium-activated potassium channel KCa3.1, encoded by the gene KCNN4, in facilitating this process. These findings offer a deeper understanding of peptide-mediated delivery using a potassium channel and raise intriguing questions about the broader implications for drug delivery strategies.

Comments

NOTICE: this is the author’s version of a work that was accepted for publication in Molecular Therapy. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Molecular Therapy in 2025. https://doi.org/10.1016/j.ymthe.2025.01.019

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The American Society of Gene and Cell Therapy

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Available for download on Wednesday, January 21, 2026

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