최정우 (서강대학교)

한빛사논문

조회189

서강대학교

CV File 142 kb

Adv. Sci., Apr 22 2024, | https://doi.org/10.1002/advs.202306432 Magnetic Nanoparticle-Assisted Non-Viral CRISPR-Cas9 for Enhanced Genome Editing to Treat Rett Syndrome

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 Lee¹

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

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

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

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

⁵School 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.

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

H.-Y.C., M.Y., and T.P. contributed equally to this work.

CORRESPONDING AUTHORS : Jeong-Woo Choi, Ki-Bum Lee

Abstract

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.

논문정보

형식Research article
게재일2024년 04월 (BRIC 등록일 2024-04-23)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 뇌인지과학

댓글 작성 로그인

CV 열람하기

연락처 보기