碱基编辑提供了一种罕见遗传病致病突变修复的可行策略
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摘要
罕见遗传病是人类医学面临的最大挑战之一,基因疗法是治疗罕见遗传病的最适方法之一。传统的基因治疗存在技术、递送和费用等方面的限制。基因编辑,特别是最近发展起来的碱基编辑技术,由于高效、准确、安全,使得早期胚胎的基因编辑逐渐被接受,从而使得通过胚胎基因编辑对罕见遗传病的致病突变进行修复成为可能。并且,由于具备合理、有效、经济、可靠等优势,基于碱基编辑修复致病突变的早期胚胎基因治疗注定将成为某些罕见遗传病的可行的、不可替代的治疗策略。为了早日实现临床胚胎基因治疗,需要进一步完善现有的技术,并加紧临床前实验。同时,通过改良监管审批程序,以及建立共享平台和共性技术等,可以进一步降低罕见遗传病的基因治疗费用。
Rare disease is one of the biggest medicine challenges. Therefore, gene therapy is considered as the most appropriate treatment. However, gene therapy has long been limited by the technology, delivery,cost, etc. Recent developed genome editing, especially the base editing characterized with efficient, accurate and safe base substitution, makes genome precise editing in human early embryos feasible, which provides the potential to correct the pathogenic mutation of rare inherited disease. Furthermore, base editing-based early embryos gene therapy is easily developed and cheap. All of these confer it as one of the most suitable strategies for the rare inherited diseases. Nevertheless, to demonstrate the future potential of embryos gene therapy in rare inherited diseases, it is extremely expected to improve current technology, to carefully perform the preclinical test. Meanwhile, to reduce the cost, it is necessary to approve standard procedures, to build sharing platforms, and to develop common technologies, etc.
Rare disease is one of the biggest medicine challenges. Therefore, gene therapy is considered as the most appropriate treatment. However, gene therapy has long been limited by the technology, delivery,cost, etc. Recent developed genome editing, especially the base editing characterized with efficient, accurate and safe base substitution, makes genome precise editing in human early embryos feasible, which provides the potential to correct the pathogenic mutation of rare inherited disease. Furthermore, base editing-based early embryos gene therapy is easily developed and cheap. All of these confer it as one of the most suitable strategies for the rare inherited diseases. Nevertheless, to demonstrate the future potential of embryos gene therapy in rare inherited diseases, it is extremely expected to improve current technology, to carefully perform the preclinical test. Meanwhile, to reduce the cost, it is necessary to approve standard procedures, to build sharing platforms, and to develop common technologies, etc.
引文
[1]Ekins S.Industrializing rare disease therapy discovery and development.Nat Biotechnol,2017,35(2):117-118
[2]Boycott KM,Ardigo D.Addressing challenges in the diagnosis and treatment of rare genetic diseases.Nat Rev Drug Discov,2018,17(3):151-152
[3]Melnikova I.Rare diseases and orphan drugs.Nat Rev Drug Discov,2012,11(4):267-268
[4]Dunbar CE,High KA,Joung JK,et al.Gene therapy comes of age.Science,2018,359(6372):eaan4672
[5]King A.Gene therapy:A new chapter.Nature,2016,537(7621):S158-159
[6]Baruteau J,Waddington SN,Alexander IE,et al.Gene therapy for monogenic liver diseases:clinical successes,current challenges and future prospects.J Inherit Metab Dis,2017,40(4):497-517
[7]Naldini L.Gene therapy returns to centre stage.Nature,2015,526(7573):351-360
[8]Collins FS,Gottlieb S.The next phase of human gene-therapy oversight.N Engl J Med,2018,379(15):1393-1395
[9]Brody H.Gene therapy.Nature,2018,564(7735):S5
[10]Mullard A.Novartis grows its gene therapy ambitions.Nat Rev Drug Discov,2018,17(5):307
[11]Platt FM.Emptying the stores:lysosomal diseases and therapeutic strategies.Nat Rev Drug Discov,2018,17(2):133-150
[12]Muench DE,Grimes HL.Transcriptional control of stem and progenitor potential.Curr Stem Cell Rep,2015,1(3):139-150
[13]Gentner B,Visigalli I,Hiramatsu H,et al.Identification of hematopoietic stem cell-specific miRNAs enables gene therapy of globoid cell leukodystrophy.Sci Transl Med,2010,2(58):58ra84
[14]Visigalli I,Delai S,Politi LS,et al.Gene therapy augments the efficacy of hematopoietic cell transplantation and fully corrects mucopolysaccharidosis type I phenotype in the mouse model.Blood,2010,116(24):5130-5139
[15]Cartier N,Hacein-Bey-Abina S,Bartholomae CC,et al.Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy.Science,2009,326(5954):818-823
[16]Biffi A,Montini E,Lorioli L,et al.Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy.Science,2013,341(6148):1233158
[17]Yin H,Kauffman KJ,Anderson DG.Delivery technologies for genome editing.Nat Rev Drug Discov,2017,16(6):387-399
[18]Orkin SH,Reilly P.MEDICINE.Paying for future success in gene therapy.Science,2016,352(6289):1059-1061
[19]Liang P,Xu Y,Zhang X,et al.CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes.Protein Cell,2015,6(5):363-372
[20]Kaiser J.A yellow light for embryo editing.Science,2017,355(6326):675
[21]Pei D,Beier DW,Levy-Lahad E,et al.Human embryo editing:opportunities and importance of transnational cooperation.Cell Stem Cell,2017,21(4):423-426
[22]Ma H,Marti-Gutierrez N,Park SW,et al.Correction of a pathogenic gene mutation in human embryos.Nature,2017,548(7668):413-419
[23]Church G.Compelling reasons for repairing human germlines.N Engl J Med,2017,377(20):1909-1911
[24]Gaudelli NM,Komor AC,Rees HA,et al.Programmable base editing of A*T to G*C in genomic DNA without DNA cleavage.Nature,2017,551(7681):464-471
[25]Komor AC,Kim YB,Packer MS,et al.Programmable editing of a target base in genomic DNA without doublestranded DNA cleavage.Nature,2016,533(7603):420-424
[26]Argmann CA,Houten SM,Zhu J,et al.A next generation multiscale view of inborn errors of metabolism.Cell Metab,2016,23(1):13-26
[2]Boycott KM,Ardigo D.Addressing challenges in the diagnosis and treatment of rare genetic diseases.Nat Rev Drug Discov,2018,17(3):151-152
[3]Melnikova I.Rare diseases and orphan drugs.Nat Rev Drug Discov,2012,11(4):267-268
[4]Dunbar CE,High KA,Joung JK,et al.Gene therapy comes of age.Science,2018,359(6372):eaan4672
[5]King A.Gene therapy:A new chapter.Nature,2016,537(7621):S158-159
[6]Baruteau J,Waddington SN,Alexander IE,et al.Gene therapy for monogenic liver diseases:clinical successes,current challenges and future prospects.J Inherit Metab Dis,2017,40(4):497-517
[7]Naldini L.Gene therapy returns to centre stage.Nature,2015,526(7573):351-360
[8]Collins FS,Gottlieb S.The next phase of human gene-therapy oversight.N Engl J Med,2018,379(15):1393-1395
[9]Brody H.Gene therapy.Nature,2018,564(7735):S5
[10]Mullard A.Novartis grows its gene therapy ambitions.Nat Rev Drug Discov,2018,17(5):307
[11]Platt FM.Emptying the stores:lysosomal diseases and therapeutic strategies.Nat Rev Drug Discov,2018,17(2):133-150
[12]Muench DE,Grimes HL.Transcriptional control of stem and progenitor potential.Curr Stem Cell Rep,2015,1(3):139-150
[13]Gentner B,Visigalli I,Hiramatsu H,et al.Identification of hematopoietic stem cell-specific miRNAs enables gene therapy of globoid cell leukodystrophy.Sci Transl Med,2010,2(58):58ra84
[14]Visigalli I,Delai S,Politi LS,et al.Gene therapy augments the efficacy of hematopoietic cell transplantation and fully corrects mucopolysaccharidosis type I phenotype in the mouse model.Blood,2010,116(24):5130-5139
[15]Cartier N,Hacein-Bey-Abina S,Bartholomae CC,et al.Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy.Science,2009,326(5954):818-823
[16]Biffi A,Montini E,Lorioli L,et al.Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy.Science,2013,341(6148):1233158
[17]Yin H,Kauffman KJ,Anderson DG.Delivery technologies for genome editing.Nat Rev Drug Discov,2017,16(6):387-399
[18]Orkin SH,Reilly P.MEDICINE.Paying for future success in gene therapy.Science,2016,352(6289):1059-1061
[19]Liang P,Xu Y,Zhang X,et al.CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes.Protein Cell,2015,6(5):363-372
[20]Kaiser J.A yellow light for embryo editing.Science,2017,355(6326):675
[21]Pei D,Beier DW,Levy-Lahad E,et al.Human embryo editing:opportunities and importance of transnational cooperation.Cell Stem Cell,2017,21(4):423-426
[22]Ma H,Marti-Gutierrez N,Park SW,et al.Correction of a pathogenic gene mutation in human embryos.Nature,2017,548(7668):413-419
[23]Church G.Compelling reasons for repairing human germlines.N Engl J Med,2017,377(20):1909-1911
[24]Gaudelli NM,Komor AC,Rees HA,et al.Programmable base editing of A*T to G*C in genomic DNA without DNA cleavage.Nature,2017,551(7681):464-471
[25]Komor AC,Kim YB,Packer MS,et al.Programmable editing of a target base in genomic DNA without doublestranded DNA cleavage.Nature,2016,533(7603):420-424
[26]Argmann CA,Houten SM,Zhu J,et al.A next generation multiscale view of inborn errors of metabolism.Cell Metab,2016,23(1):13-26