Gene therapy with induced pluripotent stem cells:a hope for beta thalassemia? / 中国组织工程研究

ABSTRACT

BACKGROUND: Beta thalassaemia is a monogenic disease, which lacks effective clinical treatments. Hematopoieticstem cell transplantation currently is the only radical treatment for beta thalassaemia, but the limits of suitable donor and costs minimize its clinical application. Given the technology of reprogramming using somatic cells is well established,gene therapy using induced pluripotent stem cells has become the new direction of beta thalassaemia treatment.OBJECTIVE: To put forward the advantages of CRISPR/Cas9 technology in gene therapy of beta thalassaemia in thefuture by summarizing the mechanisms of three kinds of gene editing technologies and the preliminary experimentalresults in animal models.METHODS: In order to search relevant articles about beta thalassaemia, the first author retrieved PubMed database andCNKI (from 1989 to 2015) using the key words of beta thalassemia, genetic therapy, genome editing, homologousrecombination, iPSCs in English and Chinese, respectively. After eliminating literatures which were irrelevant toresearch purpose or containing a similar content, 67 articles were chosen for further analysis.RESULTS AND CONCLUSION: Gene editing technology has made considerable progress and three kinds of directedgene editing technologies have been developed, including ZFNs, TALENs, CRISPR/Cas technology. By targeting inducedpluripotent stem cells from thalassemi patients, these three kinds of gene editing technologies have been expected tocorrect pathogenic genes of thalassemia. The CRISPR/Cas system is more simple, rapid, safe and efficient than the others.The CRISPR/Cas9 system is expected to repair β-globin genes in the induced pluripotent stem cells, germ cells, fertilizedeggs and embryos from beta thalassaemia patients, laying the foundation for future clinical application.