Mirror‐Image Oligonucleotides: History and Emerging Applications Academic Article uri icon


  • As chiral molecules, naturally occurring d-oligonucleotides have enantiomers, l-DNA and l-RNA, which are comprised of l-(deoxy)ribose sugars. These mirror-image oligonucleotides have the same physical and chemical properties as that of their native d-counterparts, yet are highly orthogonal to the stereospecific environment of biology. Consequently, l-oligonucleotides are resistant to nuclease degradation and many of the off-target interactions that plague traditional d-oligonucleotide-based technologies; thus making them ideal for biomedical applications. Despite a flurry of interest during the early 1990s, the inability of d- and l-oligonucleotides to form contiguous Watson-Crick base pairs with each other has ultimately led to the perception that l-oligonucleotides have only limited utility. Recently, however, scientists have begun to uncover novel strategies to harness the bio-orthogonality of l-oligonucleotides, while overcoming (and even exploiting) their inability to Watson-Crick base pair with the natural polymer. Herein, a brief history of l-oligonucleotide research is presented and emerging l-oligonucleotide-based technologies, as well as their applications in research and therapy, are presented.

altmetric score

  • 3.85

author list (cited authors)

  • Young, B. E., Kundu, N., & Sczepanski, J. T.

citation count

  • 14

complete list of authors

  • Young, Brian E||Kundu, Nandini||Sczepanski, Jonathan T

publication date

  • April 2019