Title:CRISPR/Cas9 Technology as a Modern Genetic Manipulation Tool for Recapitulating of Neurodegenerative Disorders in Large Animal Models
Volume: 21
Issue: 2
关键词:
CRISPR / Cas9，大型动物模型，神经退行性疾病，基因组编辑，临床应用，帕金森氏病。
摘要:
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 the 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 similar to humans; hence, they establish suitable models for recapitulating the
main human’s neuropathological manifestations that may not be seen in rodent models. In addition, 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.
Methods: In this review, we recommend different strategies based on the CRISPR-Cas9 system for
generating animal models of human neurodegenerative disorders and explaining in vivo CRISPR-Cas9
delivery procedures 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 the 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.
