Advancing drug discovery: creating new iPSC reporter lines through genome editing
Presenting author: Christina Kuhn1
Co-authors: Lucia Rutigliano1, Katharina Montag1, Silvia Cainarca1, Anja Nitzsche2, Pascal Röderer2, Andrea Faedo1, Paola Tarroni1, Simone Haupt2, Lia Scarabottolo1
1Axxam SpA, Via A. Meucci 3, 20091 Bresso, Milano, Italy
2LIFE& BRAIN GmbH, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany
Abstract
Human iPSC-derived models hold great promise for drug discovery especially in fields of complex diseases. However, technical problems still limit their use. It remains difficult to introduce defined changes and to achieve complete differentiation of iPSCs into for example sensory neurons (SNs). Here, we report the generation of novel reporter systems for in vitro modelling of pain through efficient genome editing of iPSCs. Insertions of fluorescent protein genes into the genomic loci of cellular markers can help visualize the differentiation process while introduction of a calcium biosensor into a safe harbour locus provides a means to analyse pain receptor function in iPSC-derived SNs. The edited iPSC lines show accurate genomic modifications without evident genomic rearrangements. They also retain stem cell markers, can be differentiated into SNs, and show functional expression. Thus, genome editing of iPSCs has great potential to significantly advance the drug discovery field.