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文献精选 > 高引权威"CRISPR基因编辑"文献

Engineering the Delivery System for CRISPR-Based Genome Editing. ​

文献信息 ​

DOI10.1016/j.tibtech.2017.11.006
PMID29305085
期刊Trends in biotechnology
影响因子14.9
JCR 分区Q1
发表年份2018
被引次数155
关键词CRISPR, Cas9, 临床, 递送, 基因编辑
文献类型Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Review
ISSN0167-7799
页码173-185
期号36(2)
作者Zachary Glass, Matthew Lee, Yamin Li, Qiaobing Xu

一句话小结 ​

本研究回顾了当前针对CRISPR-Cas基因编辑组件的体内递送策略，强调了有效运输这些组件到目标细胞核的重要性及其在治疗性基因组编辑中的应用潜力。研究指出，尽管CRISPR-Cas系统在纠正致病突变方面展现出巨大希望，但在临床应用之前仍需克服多项挑战。

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CRISPR · Cas9 · 临床 · 递送 · 基因编辑

摘要 ​

簇状规律间隔短回文重复序列-CRISPR相关蛋白（CRISPR-Cas）系统是在自然界中作为微生物适应性免疫系统存在的，现已被重新利用为生物工程和基因组编辑中的重要工具，提供了一种可编程的平台用于精准基因靶向。这些工具在作为治疗药物方面具有巨大的潜力，能够纠正致病突变。然而，CRISPR-Cas基因编辑组件必须直接运输到目标细胞的细胞核中才能发挥治疗效果。因此，交付的高效方法对于治疗性基因组编辑应用的成功至关重要。在这里，我们回顾了当前可用于体内递送CRISPR-Cas基因编辑组件的策略，并概述了在该强大工具能够在临床中应用之前需要解决的挑战。

英文摘要 ​

Clustered regularly interspaced short palindromic repeat-CRISPR-associated protein (CRISPR-Cas) systems, found in nature as microbial adaptive immune systems, have been repurposed into an important tool in biological engineering and genome editing, providing a programmable platform for precision gene targeting. These tools have immense promise as therapeutics that could potentially correct disease-causing mutations. However, CRISPR-Cas gene editing components must be transported directly to the nucleus of targeted cells to exert a therapeutic effect. Thus, efficient methods of delivery will be critical to the success of therapeutic genome editing applications. Here, we review current strategies available for in vivo delivery of CRISPR-Cas gene editing components and outline challenges that need to be addressed before this powerful tool can be deployed in the clinic.

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主要研究问题 ​

  1. 在CRISPR-Cas基因编辑中，哪些新兴的递送技术可能会改变目前的递送系统？
  2. 如何评估不同递送系统在靶向细胞核中的有效性和安全性？
  3. CRISPR基因编辑的临床应用面临哪些主要挑战，递送系统如何帮助克服这些挑战？
  4. 除了病毒载体，是否有其他非病毒递送方法在CRISPR基因编辑中表现出潜力？
  5. 递送系统的优化如何影响CRISPR-Cas基因编辑的特异性和效率？

核心洞察 ​

研究背景和目的 ​

CRISPR-Cas系统最初是微生物的适应性免疫系统，现已被重新利用为生物工程和基因组编辑的重要工具。该系统能够实现精确的基因靶向，具有作为治疗手段纠正致病突变的巨大潜力。然而，CRISPR-Cas基因编辑成分必须有效地运输到靶细胞的细胞核中，以发挥治疗效果。因此，开发高效的递送方法对于成功应用这一技术至关重要。

主要方法/材料/实验设计 ​

研究中探讨了多种CRISPR-Cas基因编辑成分的体内递送策略，包括病毒载体、非病毒载体、物理方法和化学方法。以下是递送流程的概述：

Mermaid diagram

关键结果和发现 ​

  1. CRISPR-Cas9和Cpf1的比较：Cas9利用互补RNA实现序列特异性，而Cpf1则在靶向基因时表现出更高的特异性。
  2. 递送方法的优势与挑战：
    • 病毒载体：如AAV，能够有效传递Cas9，但存在基因整合风险和包装限制。
    • 非病毒载体：提供了更大的灵活性和较低的免疫反应风险，但通常需要更复杂的递送策略。
    • 物理递送：如电穿孔和微注射，虽然在实验室中有效，但临床应用受限。
    • 化学递送：如脂质纳米颗粒，能够保护递送成分并提高靶向性，但可能面临高毒性问题。

主要结论/意义/创新性 ​

成功的CRISPR-Cas递送方法对于临床应用至关重要，特别是在治疗遗传疾病和癌症等领域。随着CRISPR技术的不断发展，未来可能出现更多的递送方法和改进，以提高递送效率、特异性和安全性。此外，CRISPR的潜在应用不仅限于基因修正，还可能扩展到抗病毒和其他治疗策略。

研究局限性和未来方向 ​

  1. 局限性：当前的递送方法仍面临许多挑战，包括有效穿透细胞膜、确保靶向递送和降低免疫反应。
  2. 未来方向：未来的研究应集中在开发更高效、更安全的递送载体，并探索CRISPR技术在新兴应用中的潜力，如针对感染性疾病的治疗。此外，结合新的递送策略和CRISPR工具（如单碱基编辑技术）将是提升基因编辑精确性和效率的关键。

通过深入探讨CRISPR-Cas的递送策略，本研究为临床基因编辑技术的推广奠定了基础。

参考文献 ​

  1. Electroporation enables the efficient mRNA delivery into the mouse zygotes and facilitates CRISPR/Cas9-based genome editing. - Masakazu Hashimoto;Tatsuya Takemoto - Scientific reports (2015)
  2. Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. - Bernd Zetsche;Jonathan S Gootenberg;Omar O Abudayyeh;Ian M Slaymaker;Kira S Makarova;Patrick Essletzbichler;Sara E Volz;Julia Joung;John van der Oost;Aviv Regev;Eugene V Koonin;Feng Zhang - Cell (2015)
  3. Expanding the Biologist's Toolkit with CRISPR-Cas9. - Samuel H Sternberg;Jennifer A Doudna - Molecular cell (2015)
  4. Highly efficient RNA-guided genome editing in human cells via delivery of purified Cas9 ribonucleoproteins. - Sojung Kim;Daesik Kim;Seung Woo Cho;Jungeun Kim;Jin-Soo Kim - Genome research (2014)
  5. CRISPR/Cas, the immune system of bacteria and archaea. - Philippe Horvath;Rodolphe Barrangou - Science (New York, N.Y.) (2010)
  6. Cancer active targeting by nanoparticles: a comprehensive review of literature. - Remon Bazak;Mohamad Houri;Samar El Achy;Serag Kamel;Tamer Refaat - Journal of cancer research and clinical oncology (2015)
  7. Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homology-directed DNA repair. - Kunwoo Lee;Michael Conboy;Hyo Min Park;Fuguo Jiang;Hyun Jin Kim;Mark A Dewitt;Vanessa A Mackley;Kevin Chang;Anirudh Rao;Colin Skinner;Tamanna Shobha;Melod Mehdipour;Hui Liu;Wen-Chin Huang;Freeman Lan;Nicolas L Bray;Song Li;Jacob E Corn;Kazunori Kataoka;Jennifer A Doudna;Irina Conboy;Niren Murthy - Nature biomedical engineering (2017)
  8. Rapid and highly efficient mammalian cell engineering via Cas9 protein transfection. - Xiquan Liang;Jason Potter;Shantanu Kumar;Yanfei Zou;Rene Quintanilla;Mahalakshmi Sridharan;Jason Carte;Wen Chen;Natasha Roark;Sridhar Ranganathan;Namritha Ravinder;Jonathan D Chesnut - Journal of biotechnology (2015)
  9. The role of dioleoylphosphatidylethanolamine (DOPE) in targeted gene delivery with mannosylated cationic liposomes via intravenous route. - Yoshiyuki Hattori;Sachiko Suzuki;Shigeru Kawakami;Fumiyoshi Yamashita;Mitsuru Hashida - Journal of controlled release : official journal of the Controlled Release Society (2005)
  10. Non-viral delivery of genome-editing nucleases for gene therapy. - M Wang;Z A Glass;Q Xu - Gene therapy (2017)

引用本文的文献 ​

  1. Fshb Knockout Mouse Model, Two Decades Later and Into the Future. - T Rajendra Kumar - Endocrinology (2018)
  2. Role of Gene Therapy in Pancreatic Cancer-A Review. - Mizuho Sato-Dahlman;Keith Wirth;Masato Yamamoto - Cancers (2018)
  3. Non-viral delivery systems for CRISPR/Cas9-based genome editing: Challenges and opportunities. - Ling Li;Shuo Hu;Xiaoyuan Chen - Biomaterials (2018)
  4. Gene editing in the context of an increasingly complex genome. - K Blighe;L DeDionisio;K A Christie;B Chawes;S Shareef;T Kakouli-Duarte;C Chao-Shern;V Harding;R S Kelly;L Castellano;J Stebbing;J A Lasky-Su;M A Nesbit;C B T Moore - BMC genomics (2018)
  5. CRISPR-Cas guides the future of genetic engineering. - Gavin J Knott;Jennifer A Doudna - Science (New York, N.Y.) (2018)
  6. CRISPR-delivery particles targeting nuclear receptor-interacting protein 1 (Nrip1) in adipose cells to enhance energy expenditure. - Yuefei Shen;Jessica L Cohen;Sarah M Nicoloro;Mark Kelly;Batuhan Yenilmez;Felipe Henriques;Emmanouela Tsagkaraki;Yvonne J K Edwards;Xiaodi Hu;Randall H Friedline;Jason K Kim;Michael P Czech - The Journal of biological chemistry (2018)
  7. DNA, RNA, and Protein Tools for Editing the Genetic Information in Human Cells. - Xiaoyu Chen;Manuel A F V Gonçalves - iScience (2018)
  8. Transfection by cationic gemini lipids and surfactants. - M Damen;A J J Groenen;S F M van Dongen;R J M Nolte;B J Scholte;M C Feiters - MedChemComm (2018)
  9. Nanoparticle-Based Delivery of CRISPR/Cas9 Genome-Editing Therapeutics. - Brittany E Givens;Youssef W Naguib;Sean M Geary;Eric J Devor;Aliasger K Salem - The AAPS journal (2018)
  10. A peptide delivery system sneaks CRISPR into cells. - Xingang Guan;Zhimin Luo;Wujin Sun - The Journal of biological chemistry (2018)

... (145 更多 篇文献)

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