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Development of an Aptamer-Based Molecular Tool for Specifically Targeting Microglia via the CD64 Protein
Hui Zhu1,2, Ende Wu1,2, Zhaoqi Pan1,2
1The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, Zhejiang325027, China.
Abstract:
Microglial dysfunction has been identified as a key factor in the pathology of several traumatic and neurodegenerative diseases in the central nervous system. Due to the importance of microglia in various pathological processes, the development of molecular tools to target microglia may be of significance for the clinical diagnosis and treatment of these disorders. In this study, a DNA aptamer, ZH-1c, that binds microglia with high affinity was developed by cell-SELEX and truncated strategies. ZH-1c exhibits promising binding ability under physiological temperatures, high serum stability after being modified, and can be internalized by microglia. Also, the binding target of ZH-1c on microglia was identified as the transmembrane protein CD64, which increased in response to inflammatory stimulation via lipopolysaccharide and interferon-gamma, thus enhancing the affinity of ZH-1c for activated microglia. Based on the above experiments, the DNA aptamer ZH-1c exhibits great potential for the targeting of activated inflammatory microglia and may be suitable as a novel and effective molecular tool for diagnosis and microglia-targeted therapies.
Insights
Researchers developed ZH-1c, a DNA aptamer targeting microglia. This tool shows potential for diagnosing and treating central nervous system disorders by targeting activated inflammatory microglia.
Area of Science:
- Neuroscience
- Biotechnology
- Molecular Biology
Background:
- Microglial dysfunction is implicated in neurodegenerative and traumatic central nervous system diseases.
- Targeting microglia is crucial for developing diagnostic and therapeutic strategies for these conditions.
Purpose of the Study:
- To develop a novel molecular tool for targeting microglia.
- To investigate the potential of DNA aptamers for diagnostic and therapeutic applications in neurological disorders.
Main Methods:
- Developed a DNA aptamer (ZH-1c) using cell-SELEX and truncation strategies.
- Assessed binding affinity, serum stability, and cellular uptake of ZH-1c.
- Identified the binding target of ZH-1c as the transmembrane protein CD64.
Main Results:
- ZH-1c demonstrated high affinity binding to microglia, particularly activated inflammatory microglia.
- The aptamer showed good binding at physiological temperatures and enhanced serum stability.
- CD64 expression increased upon inflammatory stimulation, leading to enhanced ZH-1c affinity for activated microglia.
Conclusions:
- The DNA aptamer ZH-1c is a promising molecular tool for targeting activated inflammatory microglia.
- ZH-1c has potential applications in the diagnosis and treatment of central nervous system diseases involving microglial activation.
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