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MAY 01, 2017 8:00 AM PDT

Using iPSCs and Genome Engineering to Build Disease Models

Speaker
  • Director of R&D, Cell Biology, Thermo Fisher Scientific
    Biography
      David Piper has led teams at Thermo Fisher Scientific for over 10 years in the development of products and services for cellular engineering, biochemical assays and cell-based assays for the screening of multiple target classes (ion channels, GPCRs, kinases, nuclear receptors, pathway profiling) and next generation solutions for drug discovery using iPSC-based approaches. These efforts are directed at generating more patho-physiologically relevant cell models through the use of reprogramming, stem cell culture, characterization and differentiation, genomic engineering and assay development. Currently, as an R&D Director for the Cell Biology and Synthetic Biology businesses, he leads teams that provide molecular biology and cellular biology services including cDNA Library synthesis, high-throughput cloning, CRISPR and TALN design and generation, LENTI virus generation, BacMam virus generation, cell engineering (multiple delivery and integration platforms), assay development (multiple detection formats), LentiArray™ CRISPR libraries and functional genomics screening using either siRNA or CRISPR based approaches.

    Abstract

    Developing therapies for human diseases continues to face obstacles, particularly in translating targets or compounds identified by in vitro screening campaigns to valid targets or efficacious and safe compounds once tested in humans.  Here we discuss strategies that leverage induced pluripotent stem cells (iPSCs) to increase the relevance of cell models for these in vitro approaches.  We review current advances in genome engineering and how to leverage a portfolio of these tools to generate knock-out and knock-in models for use in target or compound identification.  Specifically, we demonstrate this approach with induced pluripotent stem cells (iPSCs) to build isogenic disease models, which can be further differentiated to various cell types of interest that are more directly related to a disease area than commonly used immortalized cell lines.  We expect strategies combining genome engineering and stem cells to provide platforms for more robust disease models that will provide more predictable translation of in vitro to in vivo results.

     


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