Development of a novel genome editing method through transient arrest control of the tumor suppressor protein p53

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H02873
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 37030:Chemical biology-related
• Research Institution: Hokkaido University
• Principal Investigator: Sakaguchi Kazuyasu 北海道大学, 理学研究院, 教授 (00315053)
• Co-Investigator(Kenkyū-buntansha): 鎌田 瑠泉 北海道大学, 理学研究院, 准教授 (40750881) ; 中川 夏美 北海道大学, 理学研究院, 助教 (30881528)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 癌抑制タンパク質p53 / 多量体形成 / ゲノム編集 / ペプチド / 一過的阻害

Outline of Final Research Achievements

Genome editing has attracted significant attention as a next-generation gene therapy method. However, CRISPR/Cas9 also preferentially edits genomes of cells with dysfunctional cancer suppressor protein p53, and therefore, the development of safer and more efficient genome editing methods is required. In this study, we investigated the structural stability of p53 tetramer formation and examined the conditions for various parameters. As a result, we succeeded in significantly enhancing genome editing efficiency by transiently inhibiting p53 function through the addition of p53 tetramer formation domain peptide analogues to target cells.

Free Research Field

生物化学

Academic Significance and Societal Importance of the Research Achievements

次世代の遺伝子治療法として注目されるゲノム編集においては、高い編集効率ばかりでなく編集後の細胞癌化に対する安全性が非常に重要である。従来の方法では、編集後に細胞が癌化するリスクが懸念されていた。本研究の成果により、安全かつ高効率なゲノム編集法の改良に対しての新たな指針が示された。