范可尼贫血基因治疗研究进展

doi:10.12372/jcp.2023.21e1465

Abstract

Abstract:

Fanconi anemia is a rare monogenic disease with the hallmark of bone marrow failure. Although allogeneic hematopoietic stem cell transplantation constitutes the preferred therapy for bone marrow failure in Fanconi anemia patients, the increased incidence and mortality of transplant-related complications have seriously affected their quality of life. As medical science advances in recent 30 years, gene therapy may emerge as an innovative low-toxicity therapeutic option for this life-threatening disorder. In this paper, attention is focused on the advances in gene therapy for Fanconi anemia in children.

Key words: Fanconi anemia, gene therapy, clinical research, viral vector

XI Bixin, HU Qun, LIU Aiguo. Advances in the gene therapy for Fanconi anemia[J].Journal of Clinical Pediatrics, 2023, 41(2): 156-160.

Figures/Tables 3

References 15

[1]	Guitton-Sert L, Gao Y, Masson JY. Animal models of Fanconi anemia: A developmental and therapeutic perspective on a multifaceted disease[J]. Semin Cell Dev Biol, 2021, 55(113): 113-131.
[2]	Río P, Navarro S, Bueren JA. Advances in gene therapy for Fanconi anemia[J]. Hum Gene Ther, 2018, 29(10): 1114-1123. doi: 10.1089/hum.2018.124 pmid: 30117331
[3]	Brody H. Gene therapy[J]. Nature, 2018, 564(7735): S5. doi: 10.1038/d41586-018-07639-9
[4]	Río P, Navarro S, Wang W, et al. Successful engraftment of gene-corrected hematopoietic stem cells in non-conditioned patients with Fanconi anemia[J]. Nat Med, 2019, 25(9): 1396-1401. doi: 10.1038/s41591-019-0550-z pmid: 31501599
[5]	Liu JM, Kim S, Read EJ, et al. Engraftment of hematopoietic progenitor cells transduced with the Fanconi anemia group C gene (FANCC)[J]. Hum Gene Ther, 1999, 10(14): 2337-2346. pmid: 10515453
[6]	Hanenberg H, Roellecke K, Wiek C. Stem cell genetic therapy for fanconi anemia - a new hope[J]. Curr Gene Ther, 2017, 16(5): 309-320. doi: 10.2174/1566523217666170109111958 pmid: 28067166
[7]	Kelly PF, Radtke S, von Kalle C, et al. Stem cell collection and gene transfer in Fanconi anemia[J]. Mol Ther, 2007, 15(1): 211-219. pmid: 17164793
[8]	Gaspar HB, Parsley KL, Howe S, et al. Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector[J]. Lancet, 2004, 364(9452): 2181-2187. pmid: 15610804
[9]	Verhoeyen E, Roman-Rodriguez FJ, Cosset FL, et al. Gene therapy in Fanconi anemia: a matter of time, safety and gene transfer tool efficiency[J]. Curr Gene Ther, 2017, 16(5): 297-308. doi: 10.2174/1566523217666170109114309 pmid: 28067165
[10]	Adair JE, Chandrasekaran D, Sghia-Hughes G, et al. Novel lineage depletion preserves autologous blood stem cells for gene therapy of Fanconi anemia complementation group A[J]. Haematologica, 2018, 103(11): 1806-1814. doi: 10.3324/haematol.2018.194571 pmid: 29976742
[11]	Shafqat S, Tariq E, Parnes AD, et al. Role of gene therapy in Fanconi anemia: A systematic and literature review with future directions[J]. Hematol Oncol Stem Cell Ther, 2021, 14(4): 290-301. doi: 10.1016/j.hemonc.2021.02.001 pmid: 33736979
[12]	Shakeel S, Rajendra E, Alcón P, et al. Structure of the Fanconi anaemia monoubiquitin ligase complex[J]. Nature, 2019, 575(7781): 234-237. doi: 10.1038/s41586-019-1703-4
[13]	Sevilla J, Navarro S, Rio P, et al. Improved collection of hematopoietic stem cells and progenitors from Fanconi anemia patients for gene therapy purposes[J]. Mol Ther Methods Clin Dev, 2021, 22: 66-75. doi: 10.1016/j.omtm.2021.06.001
[14]	Czechowicz A, Rio P, Bueren JE, et al. Changing the natural history of Fanconi anemia complementation Group-A with gene therapy: early results of US Phase I study of lentiviral-mediated ex-vivo FANCA gene insertion in human stem and progenitor cells[J]. Biol Blood Marrow Transplant, 2020, 26: S39-S40.
[15]	Flotte TR, Gao G. Prime editing: a novel Cas9-reverse transcriptase fusion may revolutionize genome editing[J]. Hum Gene Ther, 2019, 30(12): 1445-1446. doi: 10.1089/hum.2019.29098.trf pmid: 31860398

临床试验编号	起止时间	载体类型	基因表型	临床试验内容	机构/国家	检索来源
NCT00001399	1993年12月─ 2009年2月	γ-逆转录病毒	FANCC	C型范科尼贫血的基因治疗	National Cancer Institute (NCI)／美国	PubMed/ ClinicalTrials.gov
NCT00005896	2000年3月─ 2005年6月	γ-逆转录病毒	FANCC	携带FANCC基因的逆转录病毒载体转导外周造血干细胞后治疗范可尼贫血	University of Minnesota／美国	ClinicalTrials.gov
NCT00272857	2004年8月─ 2007年10月	γ-逆转录病毒	FANCA	骨髓细胞基因矫正后治疗范可尼贫血	National Heart, Lung, and Blood Institute (NHLBI)／美国	PubMed/ ClinicalTrials.gov

临床试验编号	起止时间	载体类型	基因表型	临床试验内容	机构/国家	检索来源
NCT01331018	2012年2月— 2032年7月	SIN-慢病毒	FANCA	范可尼贫血的基因治疗	Fred Hutch/University of Washington Cancer Consortium／美国	文献[10]/PubMed/ ClinicalTrials.gov
NCT03157804	2016年1月— 2019年4月	PGK-慢病毒	FANCA	慢病毒介导的基因疗法治疗A型范科尼贫血(I/II期临床）	Hospital Vall d’Hebron/西班牙	文献[4]/PubMed/ ClinicalTrials.gov
NCT03351868	2017年12月— 2021年12月	SIN-慢病毒 (RP-L102)	FANCA	携带自失活设计的慢病毒载体介导FANCA基因转移来治疗范可尼贫血	首都儿科研究所附属儿童医院、北京儿童医院／中国	Clinical Trials.gov
NCT03814408	2019年1月— 2022年3月	SIN-慢病毒 (RP-L102)	FANCA	评估RP-L102介导的基因疗法治疗儿童A型范可尼贫血的安全性(I期临床）	斯坦福大学／美国	Clinical Trials.gov
NCT04069533	2019年11月— 2023年1月	SIN-慢病毒 (RP-L102)	FANCA	慢病毒介导的基因疗法治疗儿童A型范科尼贫血(Ⅱ期临床）	Hospital lnfantil Universitario Niiio Jesus (HIUNJ)／西班牙	Clinical Trials.gov
NCT04437771	2020年6月— 2035年1月	SIN-慢病毒 (RP-L102)	FANCA	儿童A型范科尼贫血基因治疗后的长期随访(I/II期临床）	Hospital lnfantil Universitario Niiio Jesus (HIUNJ)／西班牙	Clinical Trials.gov
NCT04248439	2020年7月— 2023年6月	SIN-慢病毒 (RP-L102)	FANCA	A型范科尼贫血的基因治疗(II期临床）	斯坦福大学／美国	Clinical Trials.gov

研究阶段	基因矫正策略	载体类型	基因转导	靶向的造血干细胞	基因毒性	检索来源
Ⅰ	基因添加	γ-逆转录病毒	体外（72~96 h）	CD34⁺	基因整合型	文献[6] /PubMed/ Clinical Trials.gov
Ⅱ	基因添加	SIN-慢病毒	体外（<24 h）	CD34⁺	基因整合型	文献[4, 6, 10] /PubMed/ Clinical Trials.gov
Ⅲ	基因添加	SIN-慢病毒(S/MAR)	体内	SCF-RD114	非基因整合型 S/MAR	文献[6, 9] /PubMed/ Clinical Trials.gov
Ⅳ	基因编辑	SIN-慢病毒 (CRISPR/Cas9)	体内	SCF-RD114	非基因整合型	文献[6, 9] /PubMed/ Clinical Trials.gov

Advances in the gene therapy for Fanconi anemia

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