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CRISPR/Cas9 Technology as a Modern Genetic Manipulation Tool for Recapitulating of Neurodegenerative Disorders in Large Animal Models


Mahdi Barazesh, Shiva Mohammadi*, Yadollah Bahrami*, Pooneh Mokarram, Mohammad Hossein Morowvat, Massoud Saidijam, Morteza Karimipour, Soudabe Kavousi Pour, Amir Reza Vosoughi and Korosh Khanaki   Pages 1 - 19 ( 19 )


Background: Neurodegenerative diseases are often the consequence of alterations in structures and functions of the Central Nervous System [CNS] in patients. Despite obtaining massive genomic information concerning the molecular basis of these diseases and since the neurological disorders are multifactorial, causal connections between pathological pathways at molecular level and CNS disorders development have remained obscure and need to be elucidated to a great extent.

Objective: Animal models serve as accessible and valuable tools for understanding and discovering the roles of causative factors in the development of neurodegenerative disorders and finding appropriate treatments. Contrary to rodents and other small animals, large animals especially non-human primates [NHPs] are remarkably alike humans; hence, they establish suitable models for recapitulating the main human’s neuropathological manifestations that may not be seen in rodent models. Also, they serve as useful models to discover effective therapeutic targets for neurodegenerative disorders due to their similarity to humans in terms of physiology, evolutionary distance, anatomy, and behavior.

Method: In this review, we recommend different strategies based on the CRISPR-Cas9 system for generating animal models of human neurodegenerative disorders and explain in vivo CRISPR-Cas9 delivery procedures of that are applied to disease models for therapeutic purposes.

Results: With the emergence of CRISPR/Cas9 as a modern specific gene-editing technology in the field of genetic engineering, genetic modification procedures such as gene knock-in and knock-out have become increasingly easier compared to traditional gene targeting techniques. Unlike the old techniques, this versatile technology can efficiently generate transgenic large animal models without need to complicate lab instruments. Hence, these animals can accurately replicate the signs of neurodegenerative disorders.

Conclusion: Preclinical applications of CRISPR/Cas9 gene-editing technology supply a unique opportunity to establish animal models of neurodegenerative disorders with high accuracy and facilitate perspectives for breakthroughs in the research on the nervous system disease therapy and drug discovery. Furthermore, the useful outcomes of CRISPR applications in various clinical phases are hopeful for their translation to the clinic in a short time.


CRISPR/Cas9, large animal models, neurodegenerative disorders, genome editing, clinical application.


School of Paramedical, Gerash University of Medical Sciences, Gerash, Department of Medical Biotechnology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah 6714415185, Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Department of Molecular Medicine and Genetics, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Molecular Medicine Group, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Medical Biotechnology Research Center, Paramedicine Faculty, Guilan University of Medical Sciences, Rasht

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