미래의학 - 맞춤형의학 유전자가위

Size: px

Start display at page:

Download "미래의학 - 맞춤형의학 유전자가위"

민영 종
6 years ago
Views:

1 미래의학 유전자가위 / 맞춤형의료

2 Dr. Shoukhrat Mitalipov AUGUST 2, 2017 Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, Oregon, USA Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA.

3 ARTICLE doi: /nature23305 Correction of a pathogenic gene mutation in human embryos Hong Ma 1 *, Nuria Marti-Gutierrez 1 *, Sang-Wook Park 2 *, Jun Wu 3 *, Yeonmi Lee 1, Keiichiro Suzuki 3, Amy Koski 1, Dongmei Ji 1, Tomonari Hayama 1, Riffat Ahmed 1, Hayley Darby 1, Crystal Van Dyken 1, Ying Li 1, Eunju Kang 1, A.-Reum Park 2, Daesik Kim 4, Sang-Tae Kim 2, Jianhui Gong 5,6,7,8, Ying Gu 5,6,7, Xun Xu 5,6,7, David Battaglia 1,9, Sacha A. Krieg 9, David M. Lee 9, Diana H. Wu 9, Don P. Wolf 1, Stephen B. Heitner 10, Juan Carlos Izpisua Belmonte 3, Paula Amato 1,9, Jin-Soo Kim 2,4, Sanjiv Kaul 10 & Shoukhrat Mitalipov 1,10 Genome editing has potential for the targeted correction of germline mutations. Here we describe the correction of the heterozygous MYBPC3 mutation in human preimplantation embryos with precise CRISPR Cas9-based targeting accuracy and high homology-directed repair efficiency by activating an endogenous, germline-specific DNA repair response. Induced double-strand breaks (DSBs) at the mutant paternal allele were predominantly repaired using the homologous wild-type maternal gene instead of a synthetic DNA template. By modulating the cell cycle stage at which the DSB was induced, we were able to avoid mosaicism in cleaving embryos and achieve a high yield of homozygous embryos carrying the wild-type MYBPC3 gene without evidence of off-target mutations. The efficiency, accuracy and safety of the approach presented suggest that it has potential to be used for the correction of heritable mutations in human embryos by complementing preimplantation genetic diagnosis. However, much remains to be considered before clinical applications, including the reproducibility of the technique with other heterozygous mutations.

4 MYBPC3 gene v v Chromosome 11p11.2

5 MYBPC3 돌연변이 v v v

9 가족성확장심장근육병 (familial DCM) 은관련된 30여개의유전자중어느한유전자에오류가있을경우에발생하게된다.

10 확장심장근육병 (familial DCM) 환자의 35% 가유전적요인 3억미국인구중원인불명의 DCM을가진사람이 75만명 (400명중 1명꼴 ) 비허혈성심근증을가진사람의 21% 가가족력을가지고있다.

11 DCM 치료법 v v v v

12 Newly fertilized eggs before gene editing, left, and embryos after gene editing and a few rounds of cell division. A study published on Wednesday announced that edited human embryos can repair common and serious disease-causing gene mutations.

13 Two days after being injected with a geneediting enzyme, these developing human embryos were free of a disease-causing mutation.

14 The edited embryos were allowed to develop into blastocysts, seen here.

16 Gene Editing in Embryos

17 Gene Editing in Embryos

19 CRISPR-Cas9

20 Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and CRISPR-associated (Cas) proteins CRISPR/CAS9 SYSTEM

21 Short Palindromic Sequences ( 회문구조 )

22 Spacer

23 CRISPR(CRISPR-Cas9)? v v v

24 Streptococcus pyogenes에서발견된 CRISPR-Cas9 유전자편집복합체 Cas9 핵산분해단백은가이드 RNA 염기서열을이용하여상보적 DNA를잘라낸다.

25 Cas, CRISPR associated proteins Addison V. Wright, et al. 2016, Cell

26 어떻게유전자를수정?

29 요약 : Crispr/Cas system à

30 v v v SCIENCE VOL AUGUST 2013 v v

31 어떤역할? v v v

32 CRISPR/Cas9 의응용 v v

33 NGS, Next Generation Sequencing v v v

36 Anne Wojcicki 세르게이브린

Microsoft PowerPoint - 김진수단장(IBS)자료

Microsoft PowerPoint - 김진수단장(IBS)자료 CRISPR 유전자가위로세상을바꾼다 김진수서울대학교화학부기초과학연구원유전체교정연구단 1 유전적다양성 유전자의차이가개체의차이를대부분설명함 유전자에따라질병에대한감수성이달라짐 2 유전질환 : Genetic Disorders 혈우병, 겸상적혈구증등 10,000 종이있음 전체신생아의 1% 가유전질환자임 소아과진료의 40% 에해당 대부분완치불가능 돌연변이유전자를다음세대에물려줌