期刊
GENE
卷 525, 期 2, 页码 174-181出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.gene.2013.03.098
关键词
PID; Gene therapy; HSCT; SCID; CGD; WAS
资金
- Wellcome Trust (UK)
- Great Ormond Street Hospital Children's Charity (UK)
- European Union [PERSIST 222878]
- MRC [G0501969] Funding Source: UKRI
- Great Ormond Street Hospital Childrens Charity [V1223, V1259] Funding Source: researchfish
- Medical Research Council [G0501969] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0611-10001] Funding Source: researchfish
Substantial progress has been made in the past decade in treating several primary immunodeficiency disorders (PIDs) with gene therapy. Current approaches are based on ex-vivo transfer of therapeutic transgene via viral vectors to patient-derived autologous hematopoietic stem cells (HSCs) followed by transplantation back to the patient with or without conditioning. The overall outcome from all the clinical trials targeting different PIDs has been extremely encouraging but not without caveats. Malignant outcomes from insertional mutagenesis have featured prominently in the adverse events associated with these trials and have warranted intense pre-clinical investigation into defining the tendencies of different viral vectors for genomic integration. Coupled with issues pertaining to transgene expression, the therapeutic landscape has undergone a paradigm shift in determining safety, stability and efficacy of gene therapy approaches. In this review, we aim to summarize the progress made in the gene therapy trials targeting ADA-SCID, SCID-X1, CGD and WAS, review the pitfalls, and outline the recent advancements which are expected to further enhance favourable risk benefit ratios for gene therapeutic approaches in the future. (C) 2013 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据