Cas9 Delivery: Focused Ultrasound and Nanotechnology Approaches.

IF 4.1 4区医学 Q2 GENETICS & HEREDITY

Current gene therapy Pub Date : 2026-03-19 DOI:10.2174/0115665232391997251205093227

Vatan Chaudhary, Atul Pratap Singh, Himanchal Sharma, Dhananjay Taumar, Anshu Gujjar, Iram Rajpoot

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引用次数: 0

Abstract

Introduction: CRISPR-Cas9 enables precise genome editing but faces delivery challenges, including poor cellular uptake, off-target effects, and immune activation. Focused ultrasound (FUS) and nanotechnology-based carriers offer synergistic, non-invasive solutions, enhancing delivery efficiency, tissue penetration, and targeting.

Methods: A systematic search (January 2010-March 2025) of PubMed, Web of Science, Scopus, Embase, and Google Scholar databases, preprint servers, and clinical trial registries identified studies employing FUS, nanoparticles (NPs), or combined approaches for CRISPR-Cas9 delivery. Eligible studies reported outcomes on efficiency, specificity, safety, or therapeutic effect in cell lines, animal models, or humans. Data extraction and quality assessment were performed by two independent reviewers. Narrative synthesis and meta-analysis were conducted where appropriate.

Results: Forty-eight studies (21 in vitro, 19 in vivo, 8 clinical) met the inclusion criteria. NPmediated delivery achieved ~75% editing efficiency and enhanced stability versus viral or naked methods. FUS increased tissue penetration by threefold and reduced systemic toxicity. Combined FUS-NP systems improved blood-brain barrier penetration and maintained low off-target rates (>80% of studies) with minimal immune responses.

Discussion: Hybrid FUS-NP delivery platforms address key barriers in CRISPR-Cas9 therapy, particularly for neurological, oncological, and genetic disorders. Nonetheless, heterogeneity in NP composition, ultrasound settings, and target genes limits direct comparability, and long-term clinical safety remains underexplored.

Conclusion: FUS-assisted nanotechnology provides a promising non-viral strategy for precise, safe, and targeted CRISPR-Cas9 delivery. Standardization of technical parameters and regulatory frameworks are essential for successful clinical translation.

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Cas9递送：聚焦超声和纳米技术方法。

简介：CRISPR-Cas9能够实现精确的基因组编辑，但面临递送挑战，包括细胞摄取不良、脱靶效应和免疫激活。聚焦超声（FUS）和基于纳米技术的载体提供了协同的、非侵入性的解决方案，提高了输送效率、组织渗透和靶向性。方法：系统检索PubMed、Web of Science、Scopus、Embase和谷歌Scholar数据库、预印服务器和临床试验注册库（2010年1月- 2025年3月），确定使用FUS、纳米颗粒（NPs）或联合方法进行CRISPR-Cas9递送的研究。符合条件的研究报告了在细胞系、动物模型或人类中的有效性、特异性、安全性或治疗效果。数据提取和质量评估由两名独立评审员进行。适当时进行叙事综合和元分析。结果：48项研究（21项体外研究，19项体内研究，8项临床研究）符合纳入标准。与病毒或裸方法相比，npp介导的递送达到了75%的编辑效率和更高的稳定性。FUS增加了三倍的组织穿透性，降低了全身毒性。联合FUS-NP系统提高了血脑屏障的穿透性，并在最小的免疫反应下保持低脱靶率（bbb80 %的研究）。讨论：混合FUS-NP传递平台解决了CRISPR-Cas9治疗的关键障碍，特别是神经、肿瘤和遗传疾病。尽管如此，NP组成、超声设置和靶基因的异质性限制了直接的可比性，长期临床安全性仍未得到充分探讨。结论：fus辅助纳米技术为精确、安全、靶向的CRISPR-Cas9传递提供了一种有前景的非病毒策略。技术参数和监管框架的标准化对于成功的临床翻译至关重要。

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

Current gene therapy 医学-遗传学

CiteScore

6.70

自引率

2.80%

发文量

期刊介绍： Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes full-length/mini reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases. Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.