Objective

Shortage and lack of in vitrocontrol anddisease models for the broad array of human cell types have hindered the progress in understanding and treating many diseases. Human induced Pluripotent Stem Cells (hiPSCs) are an attractive renewable cell source that can virtually generate in the dish any cell lineages from the human body, thus providing a unique advantage when primary tissues are limited or inaccessible. Consequently, hiPSCs hold great promises for establishing a powerful standard for drug development and toxicology screening. However, traditional methods of directed differentiation of hiPSCs are cumbersome, lengthy, and difficult to reproduce between labs, which is currently hindering the advancement of hiPSCs to drug discovery pipelines.

At Elpis Biomed, we have developed a robust inducible hiPSC programming technology allowing unprecedented differentiation efficiency in term of purity, scalability and reproducibility of derived human tissue. Cell programming, which takes advantage of the native regulatory role of Transcription Factors (TFs) on cell identity, is similar to rebooting a computer with a new programme to obtain a new function: hiPSCs exposed to a defined TF programme acquire a new cell identity. By dual targeting of the components of the Tet-ON 3G system into two genomic safe harbour sites (GSHs), we achieve homogenous controllable expression of master programming factors from the hiPSC stage to the differentiated cells. The introduction of each component of the Tet-ON system (the rtTA Dox-reponsive transactivator and the Tet-Operator hybrid promoter controlling transgene expression) into different GSHs enable tight control of transgene expression while allowing for increased design flexibility with the larger cargo capacity per site. Furthermore, this design reduces gene-silencing of the transgene and accordingly makes it possible for cells to be passaged extensively without changes to the differentiation potential of the cells. 

Based on this optimised dual-safe harbour technology (Elpis-OptiOX), Elpis is already offering highly pure mature cortical neurons and skeletal muscle cells obtained by the controllable induction of NGN2and MYODrespectively in hiPSCs. These Elpis-primedcells provide ready-to-assay mature differentiated human cells in only a few days, offering reliable in vitro cell models for basic and drug research. Indeed, the purity of Elpis-primedcells (>99%), their batch-to-batch consistency, ease of culture and short delay to maturity without requirements for cumbersome cell culture work have led to their successful use in very demanding screening conditions where only small changes had to be picked up from background noise. Our discovery platform is now further expanding the portfolio of cell lineages available by Elpis programming technology in order to provide additional relevant human cell models for research, target validation and high throughput drug and toxicology screenings in pharmaceutical R&D.