International journal of pharmaceuticsJan 30, 2026

Using LAH5 to deliver prime editing tools for precise genome changes

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

LAH5 may provide a non-viral way to deliver prime editor ribonucleoproteins for precise correction of the PLN R14del mutation in cells.

Evidence

This cell-line and iPSC-derived cardiomyocyte platform experiment tested LAH5 delivery of engineered SpGPEmax ribonucleoproteins in HEK293T.PLN R14del reporter cells and human iPSC-derived cardiomyocytes.

Caveat

The evidence is preclinical and limited to cellular models, so delivery performance, safety, and therapeutic efficacy in organisms or patients remain untested.

Simplified

Prime editing (PE) is a precise gene-editing technology with potential for treating genetic disorders, but efficient delivery systems remain a challenge. Viral vectors offer high efficiency but pose safety concerns related with their immunogenicity, while non-viral methods struggle with stability and scalability. Cell-penetrating peptides (CPPs) present a promising alternative due to their low immunogenicity. In this study, we explored LAH5, a histidine-rich CPP, for delivering PE ribonucleoproteins (RNPs) into PLN R14del mutant cell lines. We purified engineered SpGPEmax protein, evaluating its intracellular uptake and editing frequency in HEK293T.PLN R14del reporter cells and human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Our results demonstrate that LAH5 effectively delivers intracellularly SpGPEmax RNP components, resulting in correction of the R14del mutation, thereby offering a viable non-viral strategy for direct cellular precise genome editing.