Therapeutic oligonucleotides are powerful and versatile biopolymers developed as drugs for clinical applications due to their straightforward synthesis and design. On the other hand, many of their most promising applications require therapeutic oligonucleotides to be stable in complex biological environments such as blood and living cells. The lifetime of administered oligonucleotides can be compromised significantly in vivo due to unintended interactions, for example, with enzymes that specifically degrade bacterial or viral DNA or RNA.1
To increase biostability, researchers have developed a variety of chemically-modified nucleotide analogs and include these in therapeutic oligonucleotides. However, these chemical modifications often profoundly impact hybridization properties and can lead to increased toxicity and immunogenicity in vivo.2,3
