CRISPR Gene-Editing Models Geared Toward Therapy for Hereditary and Developmental Neurological Disorders

Frontiers in Pediatrics

Fook Choe Cheah¹  Pei Yuen Ng²  Poh Kuan Wong²  Norazrina Azmi²  Eng Wee Chua²  Saiful Effendi Syafruddin³  M. Aiman Mohtar³ 

[1] Department of Paediatrics, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia;Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia;UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia;

关键词: Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR);    gene-editing;    gene therapy;    hereditary neurological disorders;    neonates;    pharmacogenomics;    caffeine;    drug responsiveness;   

DOI  :  10.3389/fped.2021.592571

来源: Frontiers

【 摘 要 】

Hereditary or developmental neurological disorders (HNDs or DNDs) affect the quality of life and contribute to the high mortality rates among neonates. Most HNDs are incurable, and the search for new and effective treatments is hampered by challenges peculiar to the human brain, which is guarded by the near-impervious blood-brain barrier. Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR), a gene-editing tool repurposed from bacterial defense systems against viruses, has been touted by some as a panacea for genetic diseases. CRISPR has expedited the research into HNDs, enabling the generation of in vitro and in vivo models to simulate the changes in human physiology caused by genetic variation. In this review, we describe the basic principles and workings of CRISPR and the modifications that have been made to broaden its applications. Then, we review important CRISPR-based studies that have opened new doors to the treatment of HNDs such as fragile X syndrome and Down syndrome. We also discuss how CRISPR can be used to generate research models to examine the effects of genetic variation and caffeine therapy on the developing brain. Several drawbacks of CRISPR may preclude its use at the clinics, particularly the vulnerability of neuronal cells to the adverse effect of gene editing, and the inefficiency of CRISPR delivery into the brain. In concluding the review, we offer some suggestions for enhancing the gene-editing efficacy of CRISPR and how it may be morphed into safe and effective therapy for HNDs and other brain disorders.

【 授权许可】

CC BY