Enhancement of exon skipping therapy by controlling intronic sequences

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K15734
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Hyogo Medical University
• Principal Investigator: Lee Tomoko 兵庫医科大学, 医学部, 講師 (10596042)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: デュシェンヌ型筋ジストロフィー / エクソンスキッピング治療 / スプライシング / イントロン内スプライシング制御配列 / アンチセンスオリゴヌクレオチド

Outline of Final Research Achievements

Exon skipping therapies for Duchenne muscular dystrophy (DMD) require new strategies to enhance the effect. We have identified intronic splicing control sequences and verified that exon skipping efficiency can be enhanced by controlling the region. First, the intron sequences were analyzed using gDNA extracted from the peripheral blood of DMD patients with deletion mutations. Furthermore, we established a system to analyze splicing patterns using peripheral blood or muscle-derived mRNA. By examining the intron sequences and splicing patterns, we investigated the intronic splicing control sequences and the effect on the exon skipping therapy.

Free Research Field

小児神経、遺伝学

Academic Significance and Societal Importance of the Research Achievements

本研究はイントロン制御部位を新たな標的とするAS-oligoを開発しエクソン内とイントロン内の両方の制御部位を抑制することでさらに効率よくエクソンスキッピングを誘導することを目的とする独創的な研究であり、エクソキッピング治療の有効性を高め、DMDの根治治療に大きく貢献するものである。