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Stem-Engineered Aptamers with Enhanced Stability and Affinity for Tumor-Targeted Imaging.
Xuelian Cheng1,2, Fensheng Qiu1,3, Cong Cai1,2
1The Cancer Hospital of the Hangzhou Institute of Medicine (Zhejiang Cancer Hospital), The Key Laboratory of Zhejiang Province for Basic and Clinical Application of Functional Nucleic Acids, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China.
This study enhances aptamers for clinical use by engineering their stem region to resist degradation. The modified aptamer shows improved stability, binding, and tumor accumulation in preclinical models.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Development
Background:
- Aptamers offer high specificity but degrade in vivo.
- Nuclease degradation limits aptamer clinical applications.
Purpose of the Study:
- Develop a stem-engineered aptamer strategy.
- Enhance aptamer nuclease resistance and plasma stability.
- Improve aptamer efficacy for cancer targeting.
Main Methods:
- Rational engineering of aptamer stem regions.
- Incorporation of modified bases (LNA, 2'-OMe, idT).
- Secondary structure analysis and optimization.
Main Results:
- Developed MTSL1, a stabilized c-Met aptamer.
- MTSL1 shows enhanced binding affinity and plasma stability.
- MTSL1 improved cellular association and tumor accumulation in vivo.
Conclusions:
- Stem-engineered aptamers offer a promising strategy for clinical translation.
- This approach supports aptamer development for precision targeting and diagnostics.
- Optimized aptamers can overcome limitations for therapeutic applications.
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