Therapeutic antisense oligonucleotides and siRNAs can inadvertently stimulate the immune system via nucleic acid receptors, potentially interfering with their intended mechanisms of action.
May compromise ASO/siRNA efficacy via unintended immune activation; leaves open strategies to mitigate nucleic acid receptor engagement in therapeutic design.
Most of the therapeutic applications for synthetic oligodeoxynucleotides (ODN) and oligoribonucleotides (ORN) relate to mechanisms of manipulating gene expression based on Watson-Crick base pairing to endogenous nucleic acids. However, in recent years it has become apparent that the immune system has evolved defense mechanisms against infections that are based on the detection of infecting viral and bacterial nucleic acids. In some cases, synthetic ODN and ORN can trigger these defenses and, therefore, can interfere with or distort the mechanism of action of antisense ODN or small interfering RNAs.
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Richardt‐Pargmann et al. (2009) studied this question.
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