Splicing switch therapy for FCMD by utilizing genome editor system

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19457
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: Fujita Health University
• Principal Investigator: IKEDA-TANIGUCHI MARIKO (谷口真理子) 藤田医科大学, 大学病院, 准教授 (00410738)
• Co-Investigator(Kenkyū-buntansha): 斉藤 史明 帝京大学, 医学部, 教授 (40286993)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: スプライシングスイッチ / RNA / 福山型筋ジストロフィー / ゲノム編集 / アンチセンス核酸

Outline of Final Research Achievements

Fukuyama congenital muscular dystrophy (FCMD) is a prenatally-onset neuromuscular disease unique to Japan for which there is no cure. Almost all patients in Japan have splicing abnormalities caused by insertional mutations in transposon sequences that induce splicing abnormalities. We established a therapeutic platform for scarless splicing aberrations using a next-generation gene editing system, and investigated the efficiency of genome editing and its effects using an originally developed disease model. In this study, we attempted to perform genome editing without CRISPR and were able to induce silent mutations of splicing-inducing sequences in cellular systems and animal mouse models, although the efficiency was low.

Free Research Field

小児発達医学

Academic Significance and Societal Importance of the Research Achievements

福山型先天性筋ジストロフィーはスプライシング異常であり現時点では治療法がない。今後遺伝子治療や核酸治療が発展すると考えられるが、本研究では、高価な医薬品や核酸医薬、遺伝子を用いずにスプライシングを是正することが可能となる。未だに効率は低いものの本研究の成果は医療経済的にもメリットが大きいと考えられる。