Kim Huen Suk, Bernitz Jeffrey M, Lee Dung-Fang, Lemischka Ihor R
Department of Developmental and Regenerative Biology, The Black Family Stem Cell Institute , Icahn School of Medicine at Mount Sinai, New York, New York.
Stem Cells Dev. 2014 Nov 15;23(22):2673-86. doi: 10.1089/scd.2014.0167. Epub 2014 Oct 7.
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.
患者特异性诱导多能干细胞（iPSC）被认为是生物医学领域一种用途广泛的资源。由于iPSC是基于个体生成的，因此iPSC可能是用于疾病建模、药物发现以及开发患者特异性细胞疗法的最佳细胞材料。最近，为了深入了解人类病理学，患者特异性iPSC已被用于模拟人类疾病，一些iPSC衍生细胞在体外重现了病理表型。然而，复杂的多基因疾病通常并未就疾病的潜在机制得出简明结论，这在很大程度上是由于疾病状态iPSC与对照iPSC之间存在基因差异。为了规避这一问题，使用基因组编辑工具来生成完美的同基因对照正越来越受到关注。迄今为止，基于DNA结合结构域的锌指核酸酶和转录激活样效应物核酸酶已被用于在患者特异性iPSC中创建基因定义条件，一些实例已成功鉴定出疾病的新机制。随着基因组编辑工具在iPSC中的可行性和实用性不断提高，以及成簇规律间隔短回文重复序列系统的引入，了解基因组编辑工具的特点和局限性及其在iPSC技术中的应用对于拓展人类疾病建模领域至关重要。
