将腺相关病毒载体重新定向至肝外组织。

Redirecting AAV vectors to extrahepatic tissues.

作者信息

Asokan Aravind, Shen Shen

机构信息

Department of Surgery, Duke University School of Medicine, Durham, NC, USA; Department of Molecular Genetics & Microbiology, Duke University School of Medicine, Durham, NC, USA; Department of Biomedical Engineering, Duke University, Durham, NC, USA.

Vertex Pharmaceuticals, 50 Northern Avenue, Boston, MA, USA.

出版信息

Mol Ther. 2023 Dec 6;31(12):3371-3375. doi: 10.1016/j.ymthe.2023.10.005. Epub 2023 Oct 6.

DOI:10.1016/j.ymthe.2023.10.005

PMID:37805712

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10727976/

Abstract

Recombinant adeno-associated viral (AAV) vectors are the current benchmark for systemic delivery of gene therapies to multiple organs in vivo. Despite clinical successes, safe and effective gene delivery to extrahepatic tissues has proven challenging due to dose limiting toxicity arising from high liver uptake of AAV vectors. Deeper understanding of AAV structure, receptor biology, and pharmacology has enabled the design and engineering of liver-de-targeted capsids ushering in several new vector candidates. This next generation of AAVs offers significant promise for extrahepatic gene delivery to cardiovascular, musculoskeletal, and neurological tissues with improved safety profiles.

摘要

重组腺相关病毒（AAV）载体是目前在体内将基因疗法全身性递送至多个器官的基准。尽管在临床上取得了成功，但由于AAV载体在肝脏中的高摄取导致剂量限制性毒性，向肝外组织进行安全有效的基因递送已被证明具有挑战性。对AAV结构、受体生物学和药理学的更深入了解使得能够设计和改造肝脏脱靶衣壳，从而产生了几种新的载体候选物。这一代新一代AAV为向心血管、肌肉骨骼和神经组织进行肝外基因递送提供了重大希望，且安全性有所改善。