基因编辑与遗传代谢性疾病

罗小平; 应艳琴

doi:10.11852/zgetbjzz2021-0965

PDF(610 KB)

中国儿童保健杂志 ›› 2021, Vol. 29 ›› Issue (7) : 697-700. DOI: 10.11852/zgetbjzz2021-0965

专家笔谈

基因编辑与遗传代谢性疾病

罗小平, 应艳琴

作者信息 +

Genome editing and inherited metabolic disease

LUO Xiao-ping, YING Yan-qin

Author information +

文章历史 +

摘要

随着新生儿遗传代谢病筛查和二代基因测序技术的逐渐普及,越来越多的遗传代谢病在早期得到诊断。大多遗传代谢病治疗手段非常有限,基因治疗通过外源DNA序列导入,可能使遗传代谢病从基因水平彻底根治。各种基因编辑技术在遗传代谢病领域的应用均具有其优势与不足。在基因编辑技术的临床应用中需严格遵循相关的伦理制度。

Abstract

With the development and popularization of the newborn screening and second-generation sequencing techniques, more and more patients with inherited disorders were diagnosed in their early stage. For such patients, the treatment is quite limited. However, the gene therapy has been proved to be a great option to correct the mutation directly via transferring DNA to their cells. Gene editing techniques have advantages and disadvantages in their application, and related ethical issues should be strictly followed.

导出引用

罗小平, 应艳琴. 基因编辑与遗传代谢性疾病[J]. 中国儿童保健杂志. 2021, 29(7): 697-700 https://doi.org/10.11852/zgetbjzz2021-0965

LUO Xiao-ping, YING Yan-qin. Genome editing and inherited metabolic disease[J]. Chinese Journal of Child Health Care. 2021, 29(7): 697-700 https://doi.org/10.11852/zgetbjzz2021-0965

中图分类号： R722.11

参考文献

[1] Saha K,Sontheimer EJ, Brooks PJ,et al.The NIH Somatic Cell Genome Editing program[J].Nature, 2021, 592(7853): 195-204.
[2] High KA,Roncarolo MG. Gene therapy[J].N Engl J Med, 2019, 381: 455-464.
[3] Onodera M, Nelson DM, Sakiyama Y,et al. Gene therapy for severe combined immunodeficiency caused by adenosine deaminase deficiency: improved retroviral vectors for clinical trials[J]. Acta Haematol, 1999,101(2):89-96.
[4] Batshaw ML, Robinson MB, Ye X, et al. Correction of ureagenesis after gene transfer in an animal model and after liver transplantation in humans with ornithine transcarbamylase deficiency[J]. Pediatr Res, 1999, 46(5):588-593.
[5] 刘耀, 熊莹喆, 蔡镇泽, 等. 基因编辑技术的发展与挑战[J]. 生物工程学报, 2019, 35(8): 1401-1410.
[6] Chandrasegaran S, Carroll D. Origins of programmable nucleases for genome engineering[J]. J Mol Biol, 2016, 428(5): 963-989.
[7] Komor AC, Kim YB, Packer MS,et al. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage[J]. Nature,2016,533(7603):420-442.
[8] Gaudelli NM, Komor AC, Rees HA, et al. Programmable base editing of A·T to G·C in genomic DNA without DNA cleavage[J]. Nature,2017, 551(7681):464-471.
[9] Zhao D, Li J, Li S,et al. Glycosylase base editors enable C-to-A and C-to-G base changes[J]. Nat Biotechnol,2021, 39(1):35-40.
[10] Ginn SL, Amaya AK, Alexander IE, et al. Gene therapy clinical trials worldwide to 2017: Anupdate[J]. J Gene Med,2018, 20(5): e3015.
[11] Young CS,Hicks MR,Ermolova NV et al. A single crispr-cas9 deletion strategy that targets the majority of dmd patients restores dystrophin function in hipsc-derived muscle cells[J].Cell Stem Cell, 2016, 18: 533-40.
[12] Liu Y, Yang Y, Kang X,et al. One-step biallelic and scarless correction of a β-thalassemia mutation in patient-specific iPSCs without drug selection[J]. Mol Ther Nucleic Acids, 2017, 6: 57-67.
[13] Khan A, Barber DL, Huang J, et al. Lentivirus-mediated gene therapy forFabry disease[J]. Nat Commun,2021, 12(1):1178.
[14] Eichler F, Duncan C, Musolino PL,et al. Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy[J]. N Engl J Med,2017, 377(17):1630-1638.
[15] Smith BK, Collins SW, Conlon TJ, et al. Phase Ⅰ/Ⅱ trial of adeno-associated virus-mediated alpha-glucosidase gene therapy to the diaphragm for chronic respiratory failure in Pompe disease: initial safety andventilatory outcomes[J]. Hum Gene Ther,2013, 24:630-640.
[16] Corti M, Liberati C, Smith BK, et al. Safety ofintradiaphragmatic delivery of adeno-associated virus-mediated alpha-glucosidase (rAAV1-CMV-hGAA) gene therapy in children affected by Pompe disease[J]. Hum Gene Ther Clin Dev,2017, 28:208-218.
[17] Tardieu M,Zérah M, Gougeon ML, et al. Intracerebral gene therapy in children with mucopolysaccharidosis type IIIB syndrome: an uncontrolled phase 1/2 clinical trial[J]. Lancet Neurol,2017, 16(9):712-720.
[18] Savita R, Liron W, Will L et al. AAV5-factor VIII gene transfer in severe hemophilia A[J]. N Engl J Med, 2017, 377: 2519-2530.
[19] Chandler RJ, Venditti CP. Gene therapy for methylmalonic acidemia: Past, present, and future. hum gene ther. 2019, 30(10):1236-1244.
[20] Long C, McAnally JR, Shelton JM, et al. Prevention of muscular dystrophy in mice by CRISPR/Cas9-mediated editing ofgermline DNA[J]. Science,2014, 345(6201):1184-1188.
[21] Gammage PA, Viscomi C, Simard ML,et al. Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo[J]. Nat Med,2018, 24(11):1691-1695.
[22] Bacman SR, Kauppila JHK, Pereira CV, et al.MitoTALEN reduces mutant mtDNA load and restores tRNAAla levels in a mouse model of heteroplasmic mtDNA mutation[J]. Nat Med,2018, 24(11):1696-1700.
[23] Mok BY, de Moraes MH, Zeng J,et al. A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing[J]. Nature,2020, 583(7817):631-637.
[24] Liang PP, Xu YW, Zhang XY, et al. CRISPR/Cas9-mediated gene editing in humantripronuclear zygotes[J]. Prot Cell, 2015, 6(5): 363-372
[25] LaBarbera AR. Proceedings of the international summit on human gene dditing:A global discussion-Washington D.C., December 1-3, 2015[J]. J Assist Reprod Genet,2016, 33(9):1123-1127.
[26] Hruscha A, Krawitz P, Rechenberg A, et al. Efficient CRISPR/Cas9 genome editing with low off-target effects in zebrafish[J]. Development,2013, 140(24):4982-4287.
[27] Haapaniemi E, Botla S, Persson J, et al. CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response[J]. Nat Med,2018, 24(7):927-930.