Viral platform engineering for targeted gene delivery to human hematopoietic stem cells.
Viral platform engineering for targeted gene delivery to human hematopoietic stem cells.
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用于将靶向基因递送至人类造血干细胞的病毒平台工程。
DOI：
10.1016/j.ymthe.2023.11.025
复制
发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Coughlan,Lynda
中科院分区：
文献类型：
--
作者：
DelVeliz,Samanta;Coughlan,Lynda
自基因编辑技术出现以来，许多治疗方式已经通过临床前研究进入临床试验。特别是，基于CRISPR-Cas9的方法彻底改变了该领域，并为实现致病基因的治疗性靶向编辑带来了巨大希望。为了支持这一点，基于CRISPR-Cas9的疗法最近被英国和美国的监管机构（即MHRA，FDA）批准用于治疗血液病。1对于本产品，通过对含有人造血干细胞（hHSC）和祖细胞的自体CD 34+富集群体进行体内编辑来实现治疗效果。由于干细胞可以分化成不同的特化细胞，基因编辑与干细胞自我更新特性的结合对精准医学具有吸引力。然而，使用具有成本效益的递送平台来实现治疗有效载荷在体内精确靶向递送到干细胞群体的能力将代表自体患者细胞的离体基因编辑的重大进展。在本期《分子治疗》杂志中，Yao及其同事描述了一种新型人类腺病毒（HAdV）的递送平台的设计，该平台展示了干细胞体内靶向的概念证明。该方法能够在人源化小鼠中血管内（iv）施用后，将模型转基因GFP安全、有效和高度特异性地基因递送至体内长期hHSC（LT-HSC）和造血干/祖细胞（HSPC）。2作者利用各种腺病毒（Ads）的良好生物学特性，设计了基于HAdV-C5（即Ad 5）的载体，其特征在于衣壳和结构前体的遗传修饰。
Since the emergence of gene-editing technologies, numerous therapeutic modalities have advanced through pre-clinical studies and into clinical trials. In particular, CRISPR-Cas9-based approaches have revolutionized the field and hold great promise for achieving curative, targeted editing of disease-causing genes. In support of this, a CRISPR-Cas9-based therapy was recently approved by regulatory agencies in the UK and USA (ie, MHRA, FDA) for the treatment of hematologic disease. 1 For this product, the therapeutic effect is achieved byex vivoediting of autologous CD34+-enriched populations containing human hematopoietic stem cells (hHSCs) and progenitors. As stem cells can differentiate into different specialized cells, the combination of gene editing with the self-renewal properties of stem cells is appealing for precision medicine. However, the ability to use cost-effective delivery platforms to achieve precise, targeted delivery of therapeutic payloads to stem cell populations in vivo would represent a major advance on ex vivo gene editing of autologous patient cells.In this issue of Molecular Therapy, Yao and colleagues describe the design of a novel human adenovirus (HAdV)-based delivery platform that demonstrates proof of concept for in vivo targeting of stem cells. The approach enabled safe, efficient, and highly specific gene delivery of a model transgene, GFP, to long-term hHSCs (LT-HSCs) and hematopoietic stem/progenitor cells (HSPCs) in vivo after intravascular (iv) administration in humanized mice. 2 The authors capitalized on the well-characterized biology of diverse adenoviruses (Ads), and designed HAdV-C5 (ie, Ad5)-based vectors featuring genetic modifications in the capsid and structural pro-
使用工程化的 AVID 腺病毒载体平台，将基因靶向、安全、高效地递送至体内人类造血干细胞和祖细胞。
DOI：
10.1016/j.ymthe.2023.10.023
发表时间：
2024
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
Yao,Jia;Atasheva,Svetlana;Wagner,Nicole;DiPaolo,NelsonC;Stewart,PhoebeL;Shayakhmetov,DmitryM
通讯作者：
Shayakhmetov,DmitryM
英国第一个批准 CRISPR 治疗疾病：你需要知道什么
影响因子：
64.8
作者：
Carissa Wong
通讯作者：
Carissa Wong