In situ correction of various β-thalassemia mutations in human hematopoietic stem cells

分享:

简介:

论文中使用的产品/服务

Quotation shows PackGene:The AAV vector plasmids containing inverted terminal repeats (ITRs) from AAV serotype 2 (AAV2) were purchased from PackGene Biotech

Research Field:hematopoietic stem cells

AAV Serotype:AAV2, rAAV6

Targeted organ:stem cell

Animal or cell line strain:mice

询价

摘要

β-thalassemia (β-thal) is the most common monogenic disorder caused by various mutations in the human hemoglobin β (HBB) gene and affecting millions of people worldwide. Electroporation of Cas9 and single-guide RNA (sgRNA)–ribonucleoprotein (RNP) complex-mediated gene targeting in patient-derived hematopoietic stem cells (HSCs), followed by autologous transplantation, holds the promise to cure patients lacking a compatible bone marrow donor. In this study, a universal gene correction method was devised to achieve in situ correction of most types of HBB mutations by using validated CRISPR/sgRNA–RNP complexes and recombinant adeno-associated viral 6 (rAAV6) donor-mediated homology-directed repair (HDR) in HSCs. The gene-edited HSCs exhibited multi-lineage formation abilities, and the expression of β-globin transcripts was restored in differentiated erythroid cells. The method was applied to efficiently correct different mutations in β-thal patient-derived HSCs, and the edited HSCs retained the ability to engraft into the bone marrow of immunodeficient NOD-scid-IL2Rg−/− (NSI) mice. This study provides an efficient and safe approach for targeting HSCs by HDR at the HBB locus, which provides a potential therapeutic approach for treating other types of monogenic diseases in patient-specific HSCs.

关于派真

作为一家专注于AAV 技术十余年,深耕基因治疗领域的CRO&CDMO,派真生物可提供从载体设计、构建到 AAV、慢病毒和 mRNA 服务的一站式解决方案。凭借深厚的技术实力、卓越的运营管理和高标准的服务交付,我们为全球客户提供一站式CMC解决方案,包括从早期概念验证、成药性评估到IITINDBLA的各个阶段。

 

凭借我们独立知识产权的π-alphaTM 293 细胞AAV高产技术平台,我们能将AAV产量提高多至10倍,每批次产量可达1×10¹⁷vg,以满足多样化的商业化和临床项目需求。此外,我们定制化的mRNA和脂质纳米颗粒(LNP)产品及服务覆盖药物和疫苗开发的各个阶段,从研发到符合GMP的生产,提供端到端的一站式解决方案。

下载

用户登录

还没账号? 请注册
手机验证码登录
账号密码登录
手机号码*
验证码*
忘记密码?

首次使用手机号登录将自动为您注册

登录即代表阅读并接受《注册协议》 《用户协议》

新用户注册

已有账号?
手机注册
邮箱注册
手机号码*
验证码*
机构名称*
客户类型*

重置密码

手机找回密码
邮箱找回密码
手机号码*
验证码*
设置新密码*
确认新密码*