Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapieMar 20, 2026

Light-based delivery of gene-editing tools into human stem cell–derived heart cells for heart gene correction

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Photoporation may enable controllable non-viral prime-editing RNP delivery into human iPSC-derived cardiomyocytes.

Evidence

This cell-platform experiment validated delivery in HEK293T cells and iPSC-CMs, with fluorescence uptake and droplet digital PCR editing frequencies up to 8.46% under optimized conditions.

Caveat

The evidence is in vitro and reports editing feasibility, not therapeutic correction or safety in patients.

Simplified

Prime editing (PE) offers precise genome modification without inducing double-strand breaks; however, its application in cardiomyocytes remains constrained by the lack of efficient and non-integrative delivery strategies. Here, we report a tunable photoporation-based approach for the non-viral delivery of PE ribonucleoprotein (RNP) complexes into human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), a clinically relevant model for cardiac disease. Using LumiSense nanosensitizers, we first validated cytosolic delivery and editing feasibility in HEK293T cells, and subsequently achieved efficient photoporation in hard-to-transfect iPSC-CMs. Fluorescence imaging confirmed intracellular uptake of PE RNPs, and droplet digital PCR revealed prime-editing frequencies of up to 8.46% under optimized conditions. This study demonstrates a non-integrative and controllable physical strategy for PE RNP delivery into human cardiomyocytes, providing a promising foundation for the development of genome editing-based therapeutic interventions for cardiac disorders.