Magnetic Nanoparticle-Assisted Non-Viral CRISPR-Cas9 for Enhanced Genome Editing to Treat Rett Syndrome,Advanced Science

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Magnetic Nanoparticle-Assisted Non-Viral CRISPR-Cas9 for Enhanced Genome Editing to Treat Rett Syndrome
Advanced Science ( IF 14.3 ) Pub Date : 2024-04-22 , DOI: 10.1002/advs.202306432
Hyeon-Yeol Cho _{1,

2,

3} , Myungsik Yoo ₄ , Thanapat Pongkulapa ₁ , Hudifah Rabie ₁ , Alysson R Muotri ₅ , Perry T Yin ₆ , Jeong-Woo Choi ₂ , Ki-Bum Lee ₁

Affiliation

The CRISPR-Cas9 technology has the potential to revolutionize the treatment of various diseases, including Rett syndrome, by enabling the correction of genes or mutations in human patient cells. However, several challenges need to be addressed before its widespread clinical application. These challenges include the low delivery efficiencies to target cells, the actual efficiency of the genome-editing process, and the precision with which the CRISPR-Cas system operates. Herein, the study presents a Magnetic Nanoparticle-Assisted Genome Editing (MAGE) platform, which significantly improves the transfection efficiency, biocompatibility, and genome-editing accuracy of CRISPR-Cas9 technology. To demonstrate the feasibility of the developed technology, MAGE is applied to correct the mutated MeCP2 gene in induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) from a Rett syndrome patient. By combining magnetofection and magnetic-activated cell sorting, MAGE achieves higher multi-plasmid delivery (99.3%) and repairing efficiencies (42.95%) with significantly shorter incubation times than conventional transfection agents without size limitations on plasmids. The repaired iPSC-NPCs showed similar characteristics as wild-type neurons when they differentiated into neurons, further validating MAGE and its potential for future clinical applications. In short, the developed nanobio-combined CRISPR-Cas9 technology offers the potential for various clinical applications, particularly in stem cell therapies targeting different genetic diseases.

中文翻译：

磁性纳米颗粒辅助非病毒 CRISPR-Cas9 增强基因组编辑治疗雷特综合征

CRISPR-Cas9技术有潜力通过纠正人类患者细胞中的基因或突变来彻底改变包括雷特综合征在内的各种疾病的治疗。然而，在其广泛的临床应用之前，还需要解决一些挑战。这些挑战包括目标细胞的低递送效率、基因组编辑过程的实际效率以及 CRISPR-Cas 系统运行的精度。在此，该研究提出了磁性纳米粒子辅助基因组编辑（ MAGE ）平台，该平台显着提高了CRISPR-Cas9技术的转染效率、生物相容性和基因组编辑准确性。为了证明所开发技术的可行性，MAGE 被应用于纠正雷特综合征患者诱导多能干细胞衍生的神经祖细胞 (iPSC-NPC) 中突变的 MeCP2 基因。通过结合磁转染和磁激活细胞分选，MAGE 实现了更高的多质粒递送 (99.3%) 和修复效率 (42.95%)，且孵育时间明显短于传统转染剂，且不受质粒大小限制。修复后的 iPSC-NPC 在分化为神经元时表现出与野生型神经元相似的特征，进一步验证了 MAGE 及其未来临床应用的潜力。简而言之，所开发的纳米生物组合CRISPR-Cas9技术为各种临床应用提供了潜力，特别是针对不同遗传疾病的干细胞疗法。

更新日期：2024-04-22

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