Direct Comparison of d‑DNA and l‑DNA Strand-Displacement Reactions in Living Mammalian Cells Academic Article uri icon


  • To overcome technical challenges associated with the use of DNA strand-displacement circuits in vivo, including degradation by cellular nucleases, researchers are increasingly turning to bio-orthogonal l-DNA. Although enhanced stability and improved performance of l-DNA-based circuits within living cells are often implied, direct experimental evidence has not been provided. Herein, we directly compare the functional stability and kinetics of d-DNA and l-DNA strand-displacement in live cells for the first time. We show that l-DNA strand-displacement reaction systems have minimal "leak", fast reaction kinetics, and prolonged stability inside living cells as compared to conventional d-DNA. Furthermore, using "heterochiral" strand-displacement, we demonstrate that biostable l-DNA reaction components can be easily interfaced with native DNA inside cells. Overall, our results strongly support the broader adoption of l-DNA in the field of DNA molecular circuitry, especially for in vivo applications.

altmetric score

  • 3.35

author list (cited authors)

  • Zhong, W., & Sczepanski, J. T.

citation count

  • 7

complete list of authors

  • Zhong, Wenrui||Sczepanski, Jonathan T

publication date

  • January 2020