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Oligonucleotide therapeutics is a general term for molecular target agents that employ chemically synthesized oligonucleotides containing a single-stranded deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) backbone with potential specificity. These agents can inhibit gene expression or impede protein function by binding to a specific sequence of a target gene or protein [ref 1]. They, therefore, have high specificity and target molecules that cannot be controlled by conventional drugs, making it possible to develop innovative drugs against cancers and genetic diseases. Representative oligonucleotide therapeutics include antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNAs (miRNAs), aptamers and decoys.
During the preclinical development of oligonucleotides, there is a complex issue that needs to be addressed involving interaction with the innate immune system. Exogenous nucleic acids can trigger cell activation and inflammatory responses via interactions with pattern recognition receptors, including membrane-bound Toll-like receptors (TLRs) or cytosolic RIG-I family receptors (ref 33). Additionally, oligonucleotides should be evaluated for potentially undesirable interactions with blood components, such as activation of platelets, coagulation, and activation of the complement system.

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