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Chemical nucleic acid synthesis, modification and labelling

B S Sproat1

  • 1European Molecular Biology Laboratory, Heidelberg, Germany.

Current Opinion in Biotechnology
|February 1, 1993
PubMed
Summary

Solid-phase chemical synthesis of RNA is now standard, enabling the creation of modified DNA analogues. These modifications enhance nuclease resistance and cellular uptake for antisense technology applications.

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Area of Science:

  • Chemical synthesis
  • Oligonucleotide chemistry
  • Antisense technology

Background:

  • Solid-phase chemical synthesis of RNA is a routine procedure.
  • Labile protecting groups and mild deprotection methods are commonly employed.

Purpose of the Study:

  • To explore the development of modified DNA analogues for antisense technology.
  • To enhance resistance to nucleases and improve cellular uptake of therapeutic oligonucleotides.

Main Methods:

  • Chemical synthesis of RNA on solid phase.
  • Development of P-chiral phosphorothioates.
  • Synthesis of DNA analogues with modified sugars and/or backbones.

Main Results:

  • Routine chemical synthesis of RNA is achievable.
  • Development of P-chiral phosphorothioates and diverse DNA analogues.
  • Incorporation of modifier groups to enhance properties.

Conclusions:

  • Modified DNA analogues show promise for advancing antisense technology.
  • Strategies for increasing nuclease resistance and cellular uptake have been developed.

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