장혜원 (연세대학교 의과대학)

한빛사 논문

조회618

연세대학교 의과대학

CV File 161 kb

Nat. Biomed. Eng., Published 26 August 2021 | https://doi.org/10.1038/s41551-021-00788-9 Application of prime editing to the correction of mutations and phenotypes in adult mice with liver and eye diseases

Hyewon Jang^1,2,13, Dong Hyun Jo^3,13, Chang Sik Cho⁴, Jeong Hong Shin^1,2,5,6, Jung Hwa Seo^7,8, Goosang Yu ^1,2, Ramu Gopalappa ¹, Daesik Kim⁹, Sung-Rae Cho^2,7,8, Jeong Hun Kim^4,10,11,*, and Hyongbum Henry Kim ^1,2,5,6,12,*

¹Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea. ²Brain Korea 21 Plus Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea. ³Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul, Republic of Korea. ⁴Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea. ⁵Center for Nanomedicine, Institute for Basic Science (IBS), Seoul, Republic of Korea. ⁶Graduate Program of Nano Biomedical Engineering (NanoBME), Advanced Science Institute, Yonsei University, Seoul, Republic of Korea. ⁷Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. ⁸Graduate Program of NanoScience and Technology, Yonsei University, Seoul, Republic of Korea. ⁹Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea. ¹⁰Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. ¹¹Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Republic of Korea. ¹²Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea. ¹³These authors contributed equally: Hyewon Jang and Dong Hyun Jo.

^*Corresponding author.

Abstract

The use of prime editing—a gene-editing technique that induces small genetic changes without the need for donor DNA and without causing double strand breaks—to correct pathogenic mutations and phenotypes needs to be tested in animal models of human genetic diseases. Here we report the use of prime editors 2 and 3, delivered by hydrodynamic injection, in mice with the genetic liver disease hereditary tyrosinemia, and of prime editor 2, delivered by an adeno-associated virus vector, in mice with the genetic eye disease Leber congenital amaurosis. For each pathogenic mutation, we identified an optimal prime-editing guide RNA by using cells transduced with lentiviral libraries of guide-RNA-encoding sequences paired with the corresponding target sequences. The prime editors precisely corrected the disease-causing mutations and led to the amelioration of the disease phenotypes in the mice, without detectable off-target edits. Prime editing should be tested further in more animal models of genetic diseases.

논문정보

형식Research article
게재일2021년 08월 (BRIC 등록일 2021-08-27)
연구진국내 연구진
분야 의약학 > 유전 및 유전체의학

댓글 작성 로그인

CV 열람하기

연락처 보기