1. Figure 1 Chemical modifications of the ASO backbone
Figure 1 | Chemical modifications of the ASO backbone. In the past few decades a number of chemical modifications to the phosphodiester backbone have been made to improve antisense oligonucleotide (ASO) pharmacokinetic properties, tolerability profile, and target binding affinity. Phosphorothioate DNA, phosphorodiamidate morpholino (PMO), and peptide nucleic acid designs all confer resistance to nucleases and enhanced uptake in cells, resulting in increased potency of the ASO. Tricyclo-DNAs (tcDNA) are conformationally constrained DNA analogues with increased potency and enhanced uptake in tissues after systemic administration. Ribose substitutions, including 2′-O-methyl (2′-OMe), 2′-O-methoxyethyl (2′-MOE), and locked nucleic acid, are frequently used in combination to further increase stability, enhance target binding, and generally confer less toxicity than unmodified designs.
Rinaldi, C. & Wood, M. J. A. (2017) Antisense oligonucleotides: the next frontier for treatment of neurological disorders
Nat. Rev. Neurol. doi: /nrneurol