AUTHOR=Eriksson Reetta A. E. , Nieminen Tiina , Galibert Lionel , Peltola Sanna K. , Tikkanen Petra , Käyhty Piia , Leinonen Hanna M. , Oruetxebarria Igor , Lepola Saana , Valkama Anniina J. , Lipponen Eevi M. , Lesch Hanna P. , Ylä-Herttuala Seppo , Airenne Kari J. TITLE=Optimized riboswitch-regulated AAV vector for VEGF-B gene therapy JOURNAL=Frontiers in Medicine VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.1052318 DOI=10.3389/fmed.2022.1052318 ISSN=2296-858X ABSTRACT=
Gene therapy would greatly benefit from a method to regulate therapeutic gene expression temporally. Riboswitches are small RNA elements that have been studied for their potential use in turning transgene expression on or off by ligand binding. We compared several tetracycline and toyocamycin-inducible ON-riboswitches for a drug responsive transgene expression. The tetracycline-dependent K19 riboswitch showed the best control and we successfully applied it to different transgenes. The induction of gene expression was 6- to 10-fold, dose-dependent, reversible, and occurred within hours after the addition of a clinically relevant tetracycline dose, using either plasmid or adeno-associated virus (AAV) vectors. To enhance the switching capacity, we further optimized the gene cassette to control the expression of a potential therapeutic gene for cardiovascular diseases,