Magnetic Nanoparticle‐Assisted Non‐Viral CRISPR‐Cas9 for Enhanced Genome Editing to Treat Rett Syndrome

Author:

Cho Hyeon‐Yeol123ORCID,Yoo Myungsik4,Pongkulapa Thanapat1ORCID,Rabie Hudifah1,Muotri Alysson R.5ORCID,Yin Perry T.6,Choi Jeong‐Woo2ORCID,Lee Ki‐Bum1ORCID

Affiliation:

1. Department of Chemistry and Chemical Biology Rutgers, The State University of New Jersey Piscataway NJ 08854 USA

2. Department of Chemical and Biomolecular Engineering Sogang University Seoul 04107 South Korea

3. Department of Bio and Fermentation Convergence Technology Kookmin University Seoul 02707 South Korea

4. W. M. Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience Rutgers, The State University of New Jersey Piscataway NJ 08854 USA

5. School of Medicine Department of Pediatrics/Rady Children's Hospital San Diego Department of Cellular and Molecular Medicine Stem Cell Program La Jolla CA 92093 USA

6. Department of Biomedical Engineering Rutgers The State University of New Jersey Piscataway NJ 08854 USA

Abstract

AbstractThe 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.

Funder

National Science Foundation

Alzheimer's Association

Congressionally Directed Medical Research Programs

Publisher

Wiley

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