Role of CRISPR/Cas9 in the treatment of Duchenne muscular dystrophy and its delivery strategies.

Pooja Agrawal, Vancha Harish, Sharfuddin Mohd, Sachin Kumar Singh, Devesh Tewari, Ramanjireddy Tatiparthi, Sukriti Vishwas, Srinivas Sutrapu, Kamal Dua, Monica Gulati

Journal: Life sciences 2023;330():122003

PMID: 37544379

Full Text on Elsevier Science View on PubMed

Abstract

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder brought on by mutations in the DMD gene, which prevent muscle cells from expressing the dystrophin protein. CRISPR/Cas9 technology has evolved as potential option to treat DMD due to its ability to permanently skip exons, restoring the disrupted DMD reading frame and leading to dystrophin restoration. Even though, having potential to treat DMD, the delivery, safety and efficacy of this technology is still challenging. Several delivery methods, including viral vectors, nanoparticles, and electroporation, have been explored to deliver CRISPR/Cas9 to the targeted cells. Despite the potential of CRISPR/Cas9 technology in the treatment of DMD, several limitations need to be addressed. The off-target effects of CRISPR/Cas9 are a major concern that needs to be addressed to avoid unintended mutations. The delivery of CRISPR/Cas9 to the target cells and the immune response due to the viral vectors used for delivery are a few other limitations. The clinical trials of CRISPR/Cas9 for DMD provide valuable insights into the safety and efficacy of this technology in humans and the limitations that need to be known. Therefore, in this review we insightfully discussed the challenges and limitations of CRISPR/Cas9 in the treatment of DMD and delivery strategies used, and the ongoing efforts to overcome these challenges and restore dystrophin expression in DMD patients in the ongoing trials.

Address: School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India.; School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India. Electronic address: [email protected].; School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia.; Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi 110017, India.; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia; Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW 2007, Australia; Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India.

DOI: 10.1016/j.lfs.2023.122003

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MeSH Terms: Humans, Muscular Dystrophy, Duchenne, Dystrophin, CRISPR-Cas Systems, Mutation, Exons