Drug and Gene Screening –
Treating the UnTreatable

For the first time, NewStem’s Proprietary Haploid ESCs introduces expansive screenings capabilities. This advances our comprehension of human biology in health and disease as well as the identification of genes and drugs relevant for genetic and epigenetic disorders.

Identifying genes whose loss provides cells with a growth advantage under a given selective pressure. Here cells with mutations in specific genes continue to proliferate while the rest die or grow significantly slower (positive selection).

Loss of Function (LOF) mutations in essential genes are expected to result in cell death. Thus, in saturated libraries targeting mutations in all genes, those that are underrepresented or absent from the library can be identified as essential. Searching for missing clones in haploid human ESCs or their differentiated derivatives could potentially point to genes that are absolutely necessary for pluripotency or differentiation. This enhances our understanding of cell state transitions and their maintenance and allow improvement of differentiation procedures for cell based therapies in regenerative medicine.

The isolation of haploid ESCs using donor eggs carrying a genetic defect or the introduction of a specific genetic alteration into normal haploid ESCs by genome editing, prior to constructing a genome-wide library of mutant clones. Such libraries could serve in a synthetic lethality assay, where single mutations in either one of two specific genes are viable, but are lethal if co-occurring in the same cell. This type of assay may uncover functional interactions between the mutated gene of interest and any other gene in the genome, as the latter would be depleted from the library in case of synthetic lethality.

A library is generated in haploid ESCs carrying mutations associated with a specific genetic disorder. Correction of the disease phenotype can then be screened for after genome-wide mutagenesis, and genes whose LOF reverts or ameliorates this phenotype can be identified.