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Review
. 2018 Aug 1;27(R2):R89-R98.
doi: 10.1093/hmg/ddy186.

Drug screening for human genetic diseases using iPSC models

Matthew S Elitt  1 , Lilianne Barbar  1 , Paul J Tesar  1
Affiliations
Review

Drug screening for human genetic diseases using iPSC models

Matthew S Elitt et al. Hum Mol Genet. .

Abstract

Induced pluripotent stem cells (iPSCs) enable the generation of previously unattainable, scalable quantities of disease-relevant tissues from patients suffering from essentially any genetic disorder. This cellular material has proven instrumental for drug screening efforts on these disorders, and has facilitated the identification of novel therapeutics for patients. Here we will review the foundational technologies that have enabled iPSCs, the power and limitations of iPSC-based compound screens along with screening guidelines, and recent examples of screening efforts. Additionally we will provide a brief commentary on the future scientific roadmap using pluripotent- and 3D organoid-based, combinatorial approaches.

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Figures

Figure 1.
Figure 1.
A workflow detailing the four primary components of an iPSC-based compound screen along with important considerations: (1) assay development which necessitates the establishment of the cellular model and a screen-able endpoint. (2) The primary screen which involves testing either small or large compound collections to identify putative disease-modulators. (3) Secondary screening and validation which rigorously verify the efficacy and potential molecular targets of primary screening hits compound. (4) In vivo testing which confirms a compound’s efficacy and safety in a whole organism harboring disease-causative mutations.
See this image and copyright information in PMC

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