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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

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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.

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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.