Stabilization of Antisense Oligodeoxynucleotides

Unlike phosphorothioates, methylphosphonated AS-ODN are uncharged compounds with a higher cellular uptake than unmodified AS-ODN. Unfortunately, these compounds appeared to be ineffective in some cell lines. This might be explained by the formation of 

5 Delivery of Drugs and Antisense Oligonunucleotides to the Proximal Tubular Cell 

To avoid the problem of chirality and to improve the potency and limit the non-specific actions of AS-ODN, new compounds are required. Synthesis of new AS-ODNs has further improved their nuclease stability, enhanced of cellular uptake and affinity through modification of the base, sugar and phosphate moieties of the oligonucleotides [105-108], 

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Saijo Y, Perlaky L, Wang H, et al. (1994). Pharmacokinetics, tissue distribution, and stability of antisense oligodeoxynucleotide phosphorothioate ISIS 3466 in mice. Oncol. Res. 6 243-249. 

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