title: Gene correction in patient-specific iPSCs for therapy development and disease modeling.
abstract: The discovery that mature cells can be reprogrammed to become pluripotent and the development of engineered endonucleases for enhancing genome editing are two of the most exciting and impactful technology advances in modern medicine and science. Human pluripotent stem cells have the potential to establish new model systems for studying human developmental biology and disease mechanisms. Gene correction in patient-specific iPSCs can also provide a novel source for autologous cell therapy. Although historically challenging, precise genome editing in human iPSCs is becoming more feasible with the development of new genome-editing tools, including ZFNs, TALENs, and CRISPR. iPSCs derived from patients of a variety of diseases have been edited to correct disease-associated mutations and to generate isogenic cell lines. After directed differentiation, many of the corrected iPSCs showed restored functionality and demonstrated their potential in cell replacement therapy. Genome-wide analyses of gene-corrected iPSCs have collectively demonstrated a high fidelity of the engineered endonucleases. Remaining challenges in clinical translation of these technologies include maintaining genome integrity of the iPSC clones and the differentiated cells. Given the rapid advances in genome-editing technologies, gene correction is no longer the bottleneck in developing iPSC-based gene and cell therapies; generating functional and transplantable cell types from iPSCs remains the biggest challenge needing to be addressed by the research field.
authors.affiliation: Department of Oncology and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Yoon-Young
authors.initials: YY
authors.lastname: Jang
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Ross Research Building, Room 1032, 720 Rutland Ave., Baltimore, 21205, MD, USA. zye@jhmi.edu.
authors.forename: Zhaohui
authors.identifier: 0000-0001-5272-9168
authors.initials: Z
authors.lastname: Ye
mesh_terms: D000755:Anemia, Sickle Cell / Q000628:therapy; D003550:Cystic Fibrosis / Q000628:therapy; D000072669:Gene Editing; D015316:Genetic Therapy; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008954:Models, Biological; D020388:Muscular Dystrophy, Duchenne / Q000628:therapy; D044968:Regenerative Medicine; D016511:Severe Combined Immunodeficiency / Q000628:therapy; D019896:alpha 1-Antitrypsin Deficiency / Q000628:therapy; D017086:beta-Thalassemia / Q000628:therapy