講演者： Dieter C. Gruenert, Ph.D. (Professor, Department of Otolaryngology – Head and Neck Surgery Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research University of California, San Francisco)

演題： Progress toward a patient-specific, iPS cell-based comprehensive cell and gene therapy for cystic fibrosis

日時： 3月11日（火） 12:00-13:00
会場： 発生研１階カンファレンス室

抄録：
Cystic fibrosis (CF) is one of the most prevalent monogenic recessive inherited diseases in the Caucasian population and affects between 70,000 – 100,000 individuals worldwide. It is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, and has a multiorgan pathology where patients usually succumb to opportunistic lung infections. CF presents a significant health and economic burden not only on patients and their families, but also on the countries in which the patients reside. Significant progress has been made over the last several decades in refining conventional therapies for CF, however, there has been little down to address the underlying organ damage. With the advent of pluripotent stem cell technology, a new paradigm for tissue and organ repair has emerged. In this context, we have generated CF induced pluripotent stem (iPS) cells from a ∆F508/∆F508 patient. Given that these cells are pluripotent stem cells, they have both the ability to self-renew indefinitely and the ability to differentiate into any cell within the body, and thus repair/regenerate damaged organs and tissues. To ensure that the cells would be therapeutically viable, the disease causing ∆F508 mutation was corrected by gene editing with a small/short DNA fragment (SDF) donor DNA in conjunction with a transcription activator-like effector nuclease (TALEN) that introduced a sequence-specific double strand break (DSB) into the genomic (gDNA) near the target site. Clonal populations of the corrected cells were shown to have ion transport properties characteristic of wild type cells and were also able to differentiate into both cells with airway epithelial features as well as into cells with features of hematopoietic inflammatory cells – both of which are implicated in CF pathology. These studies have laid the foundation for the development of a comprehensive gene and cell therapy for CF and have significant implications for other inherited recessive disorders.

担当分野： 遺伝子機能応用学分野