Engineering adeno-associated viral vectors for CRISPR/Cas based in vivo therapeutic genome editing

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2025-04-02 DOI:10.1016/j.biomaterials.2025.123314

Buhle Moyo , Lucas B.C. Brown , Ishika I. Khondaker , Gang Bao

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Abstract

The recent approval of the first gene editing therapy for sickle cell disease and transfusion-dependent beta-thalassemia by the U.S. Food and Drug Administration (FDA) demonstrates the immense potential of CRISPR (clustered regularly interspaced short palindromic repeats) technologies to treat patients with genetic disorders that were previously considered incurable. While significant advancements have been made with ex vivo gene editing approaches, the development of in vivo CRISPR/Cas gene editing therapies has not progressed as rapidly due to significant challenges in achieving highly efficient and specific in vivo delivery. Adeno-associated viral (AAV) vectors have shown great promise in clinical trials as vehicles for delivering therapeutic transgenes and other cargos but currently face multiple limitations for effective delivery of gene editing machineries. This review elucidates these challenges and highlights the latest engineering strategies aimed at improving the efficiency, specificity, and safety profiles of AAV-packaged CRISPR/Cas systems (AAV-CRISPR) to enhance their clinical utility.

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基于体内治疗性基因组编辑的CRISPR/Cas工程腺相关病毒载体

最近，美国食品和药物管理局（FDA）批准了首个用于镰状细胞病和输血依赖性β -地中海贫血的基因编辑疗法，这表明CRISPR（聚集规律间隔短回文重复序列）技术在治疗以前被认为无法治愈的遗传疾病患者方面具有巨大潜力。虽然体外基因编辑方法取得了重大进展，但由于在实现高效和特异性体内递送方面存在重大挑战，体内CRISPR/Cas基因编辑疗法的发展并没有取得如此迅速的进展。腺相关病毒（AAV）载体在临床试验中作为递送治疗性转基因和其他货物的载体显示出巨大的前景，但目前在有效递送基因编辑机器方面面临多重限制。这篇综述阐明了这些挑战，并强调了旨在提高aav包装的CRISPR/Cas系统（AAV-CRISPR）的效率、特异性和安全性的最新工程策略，以增强其临床实用性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.