title: Genomic editing tools to model human diseases with isogenic pluripotent stem cells.
abstract: Patient-specific induced pluripotent stem cells (iPSCs) are considered a versatile resource in the field of biomedicine. As iPSCs are generated on an individual basis, iPSCs may be the optimal cellular material to use for disease modeling, drug discovery, and the development of patient-specific cellular therapies. Recently, to gain an in-depth understanding of human pathologies, patient-specific iPSCs have been used to model human diseases with some iPSC-derived cells recapitulating pathological phenotypes in vitro. However, complex multigenic diseases generally have not resulted in concise conclusions regarding the underlying mechanisms of disease, in large part due to genetic variations between disease-state and control iPSCs. To circumvent this, the use of genomic editing tools to generate perfect isogenic controls is gaining momentum. To date, DNA binding domain-based zinc finger nucleases and transcription activator-like effector nucleases have been utilized to create genetically defined conditions in patient-specific iPSCs, with some examples leading to the successful identification of novel mechanisms of disease. As the feasibility and utility of genomic editing tools in iPSCs improve, along with the introduction of the clustered regularly interspaced short palindromic repeat system, understanding the features and limitations of genomic editing tools and their applications to iPSC technology is critical to expending the field of human disease modeling.
authors: Department of Developmental and Regenerative Biology, The Black Family Stem Cell Institute , Icahn School of Medicine at Mount Sinai, New York, New York.
authors: Huen Suk
authors: HS
authors: Kim
authors: Jeffrey M
authors: JM
authors: Bernitz
authors: Dung-Fang
authors: DF
authors: Lee
authors: Ihor R
authors: IR
authors: Lemischka
mesh_terms: D005818:Genetic Engineering / Q000379:methods*; D055614:Genetic Phenomena / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*