Establishment of highly safe gene therapy without usage of double stranded DNA

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H06269
• Research Category: Grant-in-Aid for Challenging Research (Pioneering)
• Allocation Type: Single-year Grants
• Research Field: General internal medicine and related fields
• Research Institution: Hiroshima University
• Principal Investigator: Chayama Kazuaki 広島大学, 医系科学研究科(医), 教授 (00211376)
• Co-Investigator(Kenkyū-buntansha): 三木 大樹 広島大学, 医系科学研究科(医), 講師 (10584592) ; 茶山 弘美 広島大学, 医系科学研究科(医), 准教授 (70572329) ; 林 亮平 広島大学, 病院(医), 病院助教 (80772053)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: genome editing / exosome / dsDNA / cancer therapy

Outline of Final Research Achievements

Gene therapy can be used for many diseases such as hereditary diseases, cancer and viral infections. Many recessive diseases, which account for a large number of inherited diseases, restore the cell function by normalizing one site of the gene. Although gene therapyis a desirable therapy, it has been regarded as difficult to implement because there is no easy method for gene repair. Genes can be normalized by using the recently developed CRISPR / cas9 system, which is expected to make a breakthrough in gene therapy. However, the conventional methods have a risk of causing unnecessary gene modification. In this study, we attempted to perform a safe gene therapy. To perform this we established a method to express cas9 protein in normal hepatocytes.

Free Research Field

肝臓病学

Academic Significance and Societal Importance of the Research Achievements

本研究は遺伝子治療を安全性に行うという肝炎からの改良を模索したものである。dsDNAを生体に導入することなく、しかもCas9の長期的な非特異切断も防いでいる点で従来の遺伝子治療とは異なっており、Cas9を用いた遺伝子治療の応用を遺伝病のみならず癌やウイルス感染症、代謝性疾患などなど多方面に大きく広げるものとなる。遺伝子治療のもう一つの重要な要因にdeliveryがある。本研究ではそれらのいずれかを応用することを視野に入れつつ、自己の細胞から産生されるexcreted vesicle(EV)をdeliveryに用いることを考案した。