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Primer-Free Aptamer Selection Using A Random DNA Library
Published on: July 26, 2010
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A Bispecific Chimeric Aptamer Design Platform Based on c-MET Aptamer with a Replaceable Redundant Region
Xiangru Zhang1,2, Nan Zhang1,2, Haojun Sun1,3
1Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
Chembiochem : a European Journal of Chemical Biology
|June 26, 2024
Summary
Researchers engineered novel chimeric aptamers targeting cellular-mesenchymal epithelial transition factor (c-MET) for potential cancer immunotherapy. These bispecific aptamers bind c-MET and other proteins, mediating T-cell adhesion to tumor cells.
Area of Science:
- Biotechnology
- Molecular Biology
- Cancer Research
Background:
- The c-MET/HGF signaling pathway is crucial in tumor progression and metastasis.
- Aptamers offer precise molecular recognition capabilities for therapeutic development.
- Understanding aptamer-target interactions is key for molecular engineering.
Purpose of the Study:
- To engineer novel chimeric aptamers with bispecific binding capabilities.
- To investigate the binding mechanism of aptamer HF3-58 with c-MET.
- To explore the potential of engineered aptamers in cancer immunotherapy.
Main Methods:
- Cell-SELEX was used to select DNA aptamer HF3-58 targeting c-MET.
- Systematic structural and mechanistic studies of HF3-58-c-MET binding.
- Molecular engineering to replace the redundancy region of HF3-58 with other aptamers.
Main Results:
- Aptamer HF3-58 specifically binds to c-MET, with identified scaffold, recognition, and redundancy regions.
- Novel chimeric aptamers with bispecificity for c-MET and other proteins were successfully constructed.
- Chimeric aptamer HF-3b demonstrated T-cell-tumor cell adhesion, indicating potential in immunotherapy.
Conclusions:
- Aptamer HF3-58 serves as a versatile platform for developing multifunctional c-MET-targeting ligands.
- Understanding aptamer binding mechanisms guides the design of advanced functional aptamers.
- Engineered bispecific aptamers hold promise for diverse applications, including tumor immunotherapy.
