%0 Journal Article
%T Functionalized Acyclic (l)-Threoninol Nucleic Acid Four-Way Junction with High Stability In Vitro and In Vivo.
%A Märcher A
%A Kumar V
%A Andersen VL
%A El-Chami K
%A Nguyen TJD
%A Skaanning MK
%A Rudnik-Jansen I
%A Nielsen JS
%A Howard KA
%A Kjems J
%A Gothelf KV
%J Angew Chem Int Ed Engl
%V 61
%N 24
%D 06 2022 13
%M 35352451
%F 16.823
%R 10.1002/anie.202115275
%X Oligonucleotides are increasingly being used as a programmable connection material to assemble molecules and proteins in well-defined structures. For the application of such assemblies for in vivo diagnostics or therapeutics it is crucial that the oligonucleotides form highly stable, non-toxic, and non-immunogenic structures. Only few oligonucleotide derivatives fulfil all of these requirements. Here we report on the application of acyclic l-threoninol nucleic acid (aTNA) to form a four-way junction (4WJ) that is highly stable and enables facile assembly of components for in vivo treatment and imaging. The aTNA 4WJ is serum-stable, shows no non-targeted uptake or cytotoxicity, and invokes no innate immune response. As a proof of concept, we modify the 4WJ with a cancer-targeting and a serum half-life extension moiety and show the effect of these functionalized 4WJs in vitro and in vivo, respectively.