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Primer-Free Aptamer Selection Using A Random DNA Library
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A Long-Circulating Vector for Aptamers Based upon Polyphosphodiester-Backboned Molecular Brushes.

Yuyan Wang1, Dali Wang1, Jiachen Lin1

  • 1Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA.

Angewandte Chemie (International Ed. in English)
|August 18, 2022
PubMed
Summary

A novel molecular brush protects aptamers from degradation and clearance in vivo. This innovation enhances aptamer stability and bioactivity, paving the way for advanced aptamer therapeutics.

Keywords:
AnticoagulantAptamerBottlebrush PolymerOligonucleotidesPEGylation

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Area of Science:

  • Biotechnology
  • Polymer Chemistry
  • Drug Delivery

Background:

  • Aptamers, or single-stranded DNA or RNA molecules, are valuable tools in diagnostics and therapeutics.
  • However, their clinical application is limited by in vivo instability, rapid clearance, and off-target binding.
  • Developing strategies to overcome these limitations is crucial for advancing aptamer-based therapies.

Purpose of the Study:

  • To develop a novel molecular brush system to enhance the in vivo performance of aptamers.
  • To investigate the ability of a polyphosphodiester-backboned molecular brush to protect conjugated aptamers.
  • To assess the potential of this system for creating translatable aptamer-based therapeutics.

Main Methods:

  • Solid-phase synthesis was employed to assemble the aptamer conjugated to a polyphosphodiester backbone.
  • Poly(ethylene glycol) (PEG) side chains were attached using a two-step process with high efficiency.
  • The resulting molecular brush architecture allowed for precise control over polymer size and structure.

Main Results:

  • The polyphosphodiester molecular brush effectively suppressed enzymatic digestion of the aptamer.
  • Non-specific cellular uptake was reduced, and prolonged blood circulation was achieved.
  • The bioactivity of the conjugated aptamer was successfully rescued in vivo.

Conclusions:

  • The developed molecular brush system significantly improves aptamer stability and efficacy in vivo.
  • The use of generally recognized as safe building blocks enhances the therapeutic potential.
  • This approach offers a promising and translatable strategy for the development of aptamer-based therapeutics.