상세 보기
- Chae, Unbin;
- Yang, Hae-Jun;
- Kim, Hanseop;
- Lee, Seung Hwan;
- Lee, Dong Gil;
- 외 25명
WEB OF SCIENCE
3SCOPUS
4초록
Hutchinson-Gilford progeria syndrome (HGPS), an extremely rare progressive genetic disorder, is caused by a point mutation in LMNA that induces progerin production, which disrupts cellular function and triggers premature aging and mortality. Despite extensive efforts, HPGS remains incurable. We successfully implemented a strategy using RfxCas13d to selectively target progerin mRNA at specific junction regions, without unintended cleavage and reduce its expression. This technique discriminated between normal lamin A and progerin, thus providing a safe and targeted therapeutic avenue to treat HGPS. Our approach effectively restored aberrant gene expression and progerin-induced cellular phenotypes, including senescence, mitochondrial dysfunction, and DNA damage in cells with HGPS and LMNAG608G/G608G mice. Notably, LMNAG608G/G608G mice exhibited improved progeroid phenotypes, suggesting a potential therapeutic application of this approach for other diseases resulting from abnormal RNA splicing. Copyright © 2025. Published by Elsevier Inc.
키워드
- 제목
- Precise Progerin Targeting Using RfxCas13d: A Therapeutic Avenue for Hutchinson-Gilford Progeria Syndrome
- 저자
- Chae, Unbin; Yang, Hae-Jun; Kim, Hanseop; Lee, Seung Hwan; Lee, Dong Gil; Koo, Jeong Young; Ha, Seung-Min; Bak, Seo-Jong; Joo, Mina; Nam, Hyun Hee; Lim, Kyung-Seob; Kang, Philyong; Son, Hee-Chang; An, You Jeong; Kim, Young-Hyun; Song, In-Sung; Lee, Sang-Hee; Kim, Hae Rim; Cho, Sang-Mi; Kim, Eun-Kyoung; Nam, Ki-Hoan; Chung, Kyung-Sook; Kim, Jae-Yoon; Kim, Seon-Yeop; Kim, Seon-Kyu; Kim, Seon-Young; Lee, Dong-Seok; Kim, Jin-Man; Park, Young-Ho; Kim, Sun-Uk
- 발행일
- 2025-09
- 유형
- Article
- 권
- 33
- 호
- 9
- 페이지
- 4394 ~ 4413