Chemical Development of Therapeutic Oligonucleotides

: The development of several different chemical modifications of nucleic acids, with improved base-pairing affinity and specificity as well as increased resistance against nucleases, has been described. These new chemistries have allowed the synthesis of different types of therapeutic oligonucleotides. Here we discuss selected chemistries used in antisense oligonucleotide (ASO) applications (e.g., small interfering RNA (siRNA), RNase H activation, translational block, splice-switching, and also as aptamers). Recently approved oligonucleotide-based drugs are also presented briefly.