Opto-CRISPR technologies in translational neuropharmacology.
Opto-CRISPR technologies in translational neuropharmacology.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Shantou, CN · Author affiliation
Department of Biology, College of Science, Shantou University, Shantou, Guangdong, China; Xiamen Flygene Medical Technology Co., Ltd., Biomedical Industrial Park, Xiamen, Fujian, China.Location evidence
Xiamen, CN · Author affiliation
Department of Biology, College of Science, Shantou University, Shantou, Guangdong, China; Xiamen Flygene Medical Technology Co., Ltd., Biomedical Industrial Park, Xiamen, Fujian, China.Location evidence
Chongqing, CN · Author affiliation
Department of Clinical Laboratory Medicine, Chongqing University Jiangjin Hospital, Chongqing, China. Electronic address: liangqingle@126.com.Location evidence
Wuhan, CN · Author affiliation
Animal Husbandry and Veterinary Institute, Hubei Academy of Agricultural Science, Wuhan, Hubei, China; Key Laboratory of Prevention and Control Agents for Animal Bacteriosis, Ministry of Agriculture, Wuhan, Hubei, China. Electronic address: hlguorui@163.com.Location evidence
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Original abstract
Opto-CRISPR (optically controlled CRISPR/Cas) represents a major advancement in precision neurology by enabling localized gene editing within the nervous system at precise times and locations. While preclinical studies still rely largely on classical CRISPR/Cas systems, opto-CRISPR offers unprecedented opportunities to safely treat neurological diseases at their genetic roots. It achieves this by spatiotemporally correcting pathogenic mutations, halting toxic protein accumulation, repairing neurons, rebuilding neural circuitry, and accelerating drug discovery through highly realistic disease models. This review discusses this emerging field and its transformative potential for translational neuropharmacology, focusing on therapies for neurodevelopmental and neurodegenerative disorders. Opto-CRISPR is classified into four generations: Generation 1 (light-controlled Cas protein systems), Generation 2 (light-activated guide RNA systems), Generation 3 (light-controlled inhibitor systems), and Generation 4 (NIR upconversion and epigenetic multiplexing). Their working mechanisms, applications, advantages, and limitations are comprehensively described. We also critically discuss how opto-CRISPR offers distinct advantages over traditional biologics and remote modalities (e.g., small-molecule drugs, monoclonal antibodies, antisense oligonucleotides, viral-mediated gene therapy, magnetogenetics, and sonogenetics) in neuropharmacology. Finally, we address current challenges and the therapeutic outlook for the clinical translation of opto-CRISPR.