Louisiana State University and Agricultural & Mechanical College

University of Warsaw

Uniwersytet Warszawski

Ewa M Grudzien-Nogalska

Joanna Kowalska

Robert E Rhoads

Jacek Jemielity

Edward Darzynkiewicz

New RNA cap analogs are disclosed containing one or more phosphorothioates groups. The analogs also contain modifications at the 2'-O position of 7-methylguanosine that prevent them from being incorporated in the reverse orientation during in vitro synthesis of mRNA and that hence are 'anti-reverse cap analogs' (ARCAs). The ARCA modification ensures that the S atom is precisely positioned within the active sites of cap-binding proteins in both the translational and decapping machinery. The new S-ARCA analogs are resistant to in vivo decapping enzymes. Some S-ARCAs have a higher affinity for eIF4E than the corresponding analogs not containing a phosphorothioate group. When mRNAs containing the various S-ARCAs are introduced into cultured cells, some are translated as much as five-fold more efficiently than mRNAs synthesized with the conventional analog mGpppG.

Growing community of inventors

Shreveport, LA, United States of America

Ewa M Grudzien-Nogalska