Delivery of Tissue-Targeted Scalpels: Opportunities and Challenges for In Vivo CRISPR/Cas-Based Genome Editing.
Delivery of Tissue-Targeted Scalpels: Opportunities and Challenges for In Vivo CRISPR/Cas-Based Genome Editing.
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DOI：
10.1021/acsnano.0c04707
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发表时间：
2020-08-25
期刊：
影响因子：
17.1
通讯作者：
Siegwart DJ
中科院分区：
文献类型：
--
作者：
Wei T;Cheng Q;Farbiak L;Anderson DG;Langer R;Siegwart DJ
基于CRISPR/Cas9的基因组编辑已迅速成为一项强大的突破性技术，可用于生物医学研究和治疗开发的各种环境。最近对理解体外基因修饰方法的努力已经导致离体基因组编辑效率的实质性改善。由于基因组校正的疾病靶标通常位于特定器官中，因此实现基因组药物的全部潜力将需要直接在体内递送靶向特定组织和细胞的CRISPR/Cas9系统。在这方面，我们专注于CRISPR/Cas组件的体内递送进展。病毒和非病毒递送系统都有希望通过局部注射和全身注射在不同组织中进行基因编辑。我们描述了用于体内基因编辑的各种病毒载体和合成非病毒材料以及在研究和治疗模型中的应用，并总结了这两种方法迄今为止的机会和进展。我们还讨论了病毒递送的挑战，包括克服有限的包装能力，与多次给药相关的免疫原性，以及脱靶效应的可能性，以及非病毒递送，包括努力提高疗效和扩大非病毒载体在肝外组织和癌症中的应用。展望未来，将需要在用于组织和细胞类型特异性基因编辑的病毒和非病毒递送系统的安全性和效率方面取得更多进展，以实现广泛的临床转化。我们提供了用于体内基因组编辑的当前递送系统的总结，根据给药途径进行组织，并强调了生物医学研究和应用的直接机会。此外，我们还讨论了CRISPR/Cas9系统体内递送的当前挑战，以指导未来疗法的开发。
CRISPR/Cas9-based genome editing has quickly emerged as a powerful breakthrough technology for use in diverse settings across biomedical research and therapeutic development. Recent efforts toward understanding gene modification methods in vitro have led to substantial improvements in ex vivo genome editing efficiency. Because disease targets for genomic correction are often localized in specific organs, realization of the full potential of genomic medicines will require delivery of CRISPR/Cas9 systems targeting specific tissues and cells directly in vivo. In this Perspective, we focus on progress toward in vivo delivery of CRISPR/Cas components. Viral and nonviral delivery systems are both promising for gene editing in diverse tissues via local injection and systemic injection. We describe the various viral vectors and synthetic nonviral materials used for in vivo gene editing and applications to research and therapeutic models, and summarize opportunities and progress to date for both methods. We also discuss challenges for viral delivery, including overcoming limited packaging capacity, immunogenicity associated with multiple dosing, and the potential for off-target effects, and nonviral delivery, including efforts to increase efficacy and to expand utility of nonviral carriers for use in extrahepatic tissues and cancer. Looking ahead, additional advances in the safety and efficiency of viral and nonviral delivery systems for tissue- and cell-type-specific gene editing will be required to enable broad clinical translation. We provide a summary of current delivery systems used for in vivo genome editing, organized with respect to route of administration, and highlight immediate opportunities for biomedical research and applications. Furthermore, we discuss current challenges for in vivo delivery of CRISPR/Cas9 systems to guide the development of future therapies.
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DOI：
10.1016/j.omtn.2017.10.010
发表时间：
2017-12-15
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Guo S;Li H;Ma M;Fu J;Dong Y;Guo P
通讯作者：
Guo P
影响因子：
13.6
作者：
Gaj T;Ojala DS;Ekman FK;Byrne LC;Limsirichai P;Schaffer DV
通讯作者：
Schaffer DV
影响因子：
82.9
作者：
Charlesworth, Carsten T.;Deshpande, Priyanka S.;Porteus, Matthew H.
通讯作者：
Porteus, Matthew H.
影响因子：
15
作者：
Alsaiari, Shahad K.;Patil, Sachin;Khashab, Niveen M.
通讯作者：
Khashab, Niveen M.
使用逆行病毒载体递送和体内 CRISPR/Cas9 介导的体细胞基因组编辑进行胰腺癌建模。
影响因子：
10.5
作者：
Chiou SH;Winters IP;Wang J;Naranjo S;Dudgeon C;Tamburini FB;Brady JJ;Yang D;Grüner BM;Chuang CH;Caswell DR;Zeng H;Chu P;Kim GE;Carpizo DR;Kim SK;Winslow MM
通讯作者：
Winslow MM