Title:Advances in the Synthesis and Antisense Technology Applications of Bridged Nucleic Acid Monomers
Volume: 25
Issue: 20
Author(s): Priyanka Mangla, Balaji Olety*Vivek K. Sharma*
Affiliation:
- Department of Molecular Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, 01605,United States
- MassBiologics of the University of Massachusetts Medical School, Mattapan, MA 02126,United States
Keywords:
Bridged or locked nucleic acids, antisense oligonucleotides, chemo-enzymatic synthesis, lipases, Novozyme®-435, transglycosylation
reaction.
Abstract: Bridged Nucleic Acids (BNA) or Locked Nucleic Acids (LNA) belong to a class of
nucleic acid modification that is obtained by connecting the 2'-O and 4'-C of ribose sugar using
a methylene bridge. This ‘bridging or locking’ of ribose sugar has a tremendous impact on
the biological and biophysical properties of therapeutic nucleic acids. They have enhanced
stability against nucleases and also have a higher binding affinity for the target RNA. Owing
to these advantages, BNA is one of the most preferred nucleic acids modifications of Antisense
Oligonucleotides (ASOs). However, the synthesis of BNA monomers is lengthy and
low-yielding and requires extensive protection and deprotection of the sugar functionalities. In
this article, we aim to review challenges associated with their synthesis and discuss recent
chemical, chemo-enzymatic, and transglycosylation strategies employed for the efficient and
cost-effective synthesis of BNA monomers and selected BNA analogues.