COMMENTARY

CRISPR-mediated gene editing to rescue haploinsufficient obesity syndrome

  • Zhifeng Wang 1,2 ,
  • Liu Yang 3 ,
  • Shen Qu , 3 ,
  • Chao Zhang , 1
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  • 1. Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
  • 2. Research & Development Department, Sinoneural Cell and Gene Engineering Holdings Co., Ltd., Shanghai, China
  • 3. Department of Endocrinology and Metabolism, National Metabolic Management Center, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai 200092, China

Published date: 15 Oct 2019

Copyright

2019 The Author(s)

Cite this article

Zhifeng Wang , Liu Yang , Shen Qu , Chao Zhang . CRISPR-mediated gene editing to rescue haploinsufficient obesity syndrome[J]. Protein & Cell, 2019 , 10(10) : 705 -708 . DOI: 10.1007/s13238-019-0635-y

1
Akcakaya P, Bobbin ML, Guo JA, Malagon-Lopez J, Clement K, Garcia SP, Fellows MD, Porritt MJ, Firth MA, Carreras A (2018) In vivo CRISPR editing with no detectable genome-wide off-target mutations. Nature 561:416–419

DOI

2
Amoasii L, Hildyard JCW, Li H, Sanchez-Ortiz E, Mireault A, Caballero D, Harron R, Stathopoulou TR, Massey C, Shelton JM (2018) Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy. Science 362:86–91

DOI

3
Argyropoulos G, Brown AM, Willi SM, Zhu J, He Y, Reitman M, Gevao SM, Spruill I, Garvey WT (1998) Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes. J Clin Investig 102:1345–1351

DOI

4
Asai M, Ramachandrappa S, Joachim M, Shen Y, Zhang R, Nuthalapati N, Ramanathan V, Strochlic DE, Ferket P, Linhart K (2013) Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity. Science 341:275–278

DOI

5
Bakondi B, Lv W, Lu B, Jones MK, Tsai Y, Kim KJ, Levy R, Akhtar AA, Breunig JJ, Svendsen CN (2016) In vivo CRISPR/Cas9 gene editing corrects retinal dystrophy in the S334ter-3 rat model of autosomal dominant retinitis pigmentosa. Mol Ther 24:556–563

DOI

6
Balthasar N, Dalgaard LT, Lee CE, Yu J, Funahashi H, Williams T, Ferreira M, Tang V, McGovern RA, Kenny CD (2005) Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell 123:493–505

DOI

7
Boettcher M, McManus MT (2015) Choosing the right tool for the job: RNAi, TALEN, or CRISPR. Mol Cell 58:575–585

DOI

8
Chapdelaine P, Gerard C, Sanchez N, Cherif K, Rousseau J, Ouellet DL, Jauvin D, Tremblay JP (2016) Development of an AAV9 coding for a 3XFLAG-TALEfrat#8-VP64 able to increase in vivo the human frataxin in YG8R mice. Gene Ther 23:606–614

DOI

9
Church C, Moir L, McMurray F, Girard C, Banks GT, Teboul L, Wells S, Bruning JC, Nolan PM, Ashcroft FM (2010) Overexpression of Fto leads to increased food intake and results in obesity. Nat Genet 42:1086–1092

DOI

10
Cohen J (2018) In dogs, CRISPR fixes a muscular dystrophy. Science 361:835

DOI

11
Creemers JW, Choquet H, Stijnen P, Vatin V, Pigeyre M, Beckers S, Meulemans S, Than ME, Yengo L, Tauber M (2012) Heterozygous mutations causing partial prohormone convertase 1 deficiency contribute to human obesity. Diabetes 61:383–390

DOI

12
Ding Q, Strong A, Patel KM, Ng SL, Gosis BS, Regan SN, Cowan CA, Rader DJ, Musunuru K (2014) Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing. Circ Res 115:488–492

DOI

13
Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O’Rahilly S (2003) Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med 348:1085–1095

DOI

14
Hohenstein P, Slight J, Ozdemir DD, Burn SF, Berry R, Hastie ND (2008) High-efficiency Rosa26 knock-in vector construction for Cre-regulated overexpression and RNAi. Pathogenetics 1:3

DOI

15
Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, Berkemeier LR, Gu W, Kesterson RA, Boston BA, Cone RD (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88:131–141

DOI

16
Kannisto K, Pietilainen KH, Ehrenborg E, Rissanen A, Kaprio J, Hamsten A, Yki-Jarvinen H (2004) Overexpression of 11beta-hydroxysteroid dehydrogenase-1 in adipose tissue is associated with acquired obesity and features of insulin resistance: studies in young adult monozygotic twins. J Clin Endocrinol Metab 89:4414–4421

DOI

17
Kublaoui BM, Holder JL Jr, Tolson KP, Gemelli T, Zinn AR (2006) SIM1 overexpression partially rescues agouti yellow and diet- induced obesity by normalizing food intake. Endocrinology 147:4542–4549

DOI

18
Liang P, Xu Y, Zhang X, Ding C, Huang R, Zhang Z, Lv J, Xie X, Chen Y, Li Y (2015) CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell 6:363–372

DOI

19
Liu C, Zhang L, Liu H, Cheng K (2017) Delivery strategies of the CRISPR-Cas9 gene-editing system for therapeutic applications. J Control Release 266:17–26

DOI

20
Long C, Amoasii L, Mireault AA, McAnally JR, Li H, Sanchez-Ortiz E, Bhattacharyya S, Shelton JM, Bassel-Duby R, Olson EN (2016) Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science 351:400–403

DOI

21
Ma Y, Zhang L, Huang X (2014) Genome modification by CRISPR/Cas9. FEBS J 281:5186–5193

DOI

22
Matharu N, Rattanasopha S, Tamura S, Maliskova L, Wang Y, Bernard A, Hardin A, Eckalbar WL, Vaisse C, Ahituv N (2019) CRISPR-mediated activation of a promoter or enhancer rescues obesity caused by haploinsufficiency. Science 363:eaau0629

DOI

23
Michaud JL, Boucher F, Melnyk A, Gauthier F, Goshu E, Levy E, Mitchell GA, Himms-Hagen J, Fan CM (2001) Sim1 haploinsuf- ficiency causes hyperphagia, obesity and reduction of the paraventricular nucleus of the hypothalamus. Hum Mol Genet 10:1465–1473

DOI

24
Nelson CE, Hakim CH, Ousterout DG, Thakore PI, Moreb EA, Castellanos Rivera RM, Madhavan S, Pan X, Ran FA, Yan WX (2016) In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science 351:403–407

DOI

25
Pignani S, Zappaterra F, Barbon E, Follenzi A, Bovolenta M, Bernardi F, Branchini A, Pinotti M (2019) Tailoring the CRISPR system to transactivate coagulation gene promoters in normal and mutated contexts. Biochim Biophys Acta Gene Regul Mech. https://doi.org/10.1016/j.bbagrm.2019.04.002

DOI

26
Rankinen T, Zuberi A, Chagnon YC, Weisnagel SJ, Argyropoulos G, Walts B, Perusse L, Bouchard C (2006) The human obesity gene map: the 2005 update. Obesity 14:529–644

DOI

27
Rossidis AC, Stratigis JD, Chadwick AC, Hartman HA, Ahn NJ, Li H, Singh K, Coons BE, Li L, Lv W (2018) In utero CRISPRmediated therapeutic editing of metabolic genes. Nat Med 24:1513–1518

DOI

28
Savell KE, Bach SV, Zipperly ME, Revanna JS, Goska NA, Tuscher JJ, Duke CG, Sultan FA, Burke JN, Williams D (2019) A neuron-optimized CRISPR/dCas9 activation system for robust and specific gene regulation. eNeuro.

DOI

29
Seeger C, Sohn JA (2014) Targeting hepatitis B virus with CRISPR/Cas9. Mol Ther Nucleic Acids 3:e216

DOI

30
Sera T (2009) Zinc-finger-based artificial transcription factors and their applications. Adv Drug Deliv Rev 61:513–526

DOI

31
Shah BP, Vong L, Olson DP, Koda S, Krashes MJ, Ye C, Yang Z, Fuller PM, Elmquist JK, Lowell BB (2014) MC4R-expressing glutamatergic neurons in the paraventricular hypothalamus regulate feeding and are synaptically connected to the parabrachial nucleus. Proc Natl Acad Sci USA 111:13193–13198

DOI

32
Shinohara ET, Kaminski JM, Segal DJ, Pelczar P, Kolhe R, Ryan T, Coates CJ, Fraser MJ, Handler AM, Yanagimachi R (2007) Active integration: new strategies for transgenesis. Trans Res 16:333–339

DOI

33
Soriano V (2017) Hot news: gene therapy with CRISPR/Cas9 coming to age for HIV cure. AIDS Rev 19:167–172

DOI

34
Tabebordbar M, Zhu K, Cheng JKW, Chew WL, Widrick JJ, Yan WX, Maesner C, Wu EY, Xiao R, Ran FA (2016) In vivo gene editing in dystrophic mouse muscle and muscle stem cells. Science 351:407–411

DOI

35
Vaisse C, Clement K, Durand E, Hercberg S, Guy-Grand B, Froguel P (2000) Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity. J Clin Investig 106:253–262

DOI

36
Wang L, Smith J, Breton C, Clark P, Zhang J, Ying L, Che Y, Lape J, Bell P, Calcedo R (2018) Meganuclease targeting of PCSK9 in macaque liver leads to stable reduction in serum cholesterol. Nat Biotechnol 36:717–725

DOI

37
Wang X, Raghavan A, Chen T, Qiao L, Zhang Y, Ding Q, Musunuru K (2016) CRISPR-Cas9 targeting of PCSK9 in human hepatocytes in vivo-brief report. Arterioscler Thromb Vasc Biol 36:783–786

DOI

38
Xiong L, Wu F, Wu Q, Xu L, Cheung OK, Kang W, Mok MT, Szeto LLM, Lun CY, Lung RW (2019) Aberrant enhancer hypomethylation contributes to hepatic carcinogenesis through global transcriptional reprogramming. Nat Commun 10:335

DOI

39
Xu Y, Wu Z, Sun H, Zhu Y, Kim ER, Lowell BB, Arenkiel BR, Xu Y, Tong Q (2013) Glutamate mediates the function of melanocortin receptor 4 on Sim1 neurons in body weight regulation. Cell Metab 18:860–870

DOI

40
Zou Y, Lu P, Shi J, Liu W, Yang M, Zhao S, Chen N, Chen M, Sun Y, Gao A (2017) IRX3 promotes the browning of white adipocytes and its rare variants are associated with human obesity risk. EBioMedicine 24:64–75

DOI

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