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Lipid-Nanoparticle-Based Delivery of CRISPR/Cas9 Genome-Editing Components. ​

文献信息 ​

DOI10.1021/acs.molpharmaceut.1c00916
PMID35594500
期刊Molecular pharmaceutics
影响因子4.5
JCR 分区Q1
发表年份2022
被引次数82
关键词CRISPR/Cas9, 基因治疗, 基因组编辑, 脂质纳米颗粒, 纳米医学
文献类型Journal Article, Review, Research Support, Non-U.S. Gov't
ISSN1543-8384
页码1669-1686
期号19(6)
作者Pardis Kazemian, Si-Yue Yu, Sarah B Thomson, Alexandra Birkenshaw, Blair R Leavitt, Colin J D Ross

一句话小结 ​

本综述探讨了CRISPR/Cas9基因编辑技术在治疗遗传疾病和癌症中的潜力，以及脂质纳米颗粒（LNPs）作为有效递送系统的优势与挑战。研究表明，LNPs的低免疫原性和灵活性使其成为CRISPR成分递送的理想选择，并推动了新型LNP配方的发展，为临床应用提供了重要前景。

在麦伴科研 (maltsci.com) 搜索更多文献 ​

CRISPR/Cas9 · 基因治疗 · 基因组编辑 · 脂质纳米颗粒 · 纳米医学

摘要 ​

CRISPR/Cas9系统介导的基因编辑预计将成为治疗遗传疾病和某些癌症的有益治疗选择。然而，CRISPR成分的递送面临挑战，这需要复杂的递送系统以实现安全和有效的基因组编辑。由于脂质纳米颗粒（LNPs）的低免疫原性和应用灵活性，它们已成为CRISPR介导的基因组编辑的有吸引力的非病毒递送平台。在本综述中，我们提供了关于CRISPR介导基因疗法的背景，以及LNPs及其在递送CRISPR成分方面的适用特性。接着，我们强调了CRISPR递送的挑战，这推动了过去十年中新型、安全且优化的LNP配方的显著发展。最后，我们讨论了使用LNP递送CRISPR时的注意事项以及LNP-CRISPR基因编辑临床转化的未来展望。

英文摘要 ​

Gene editing mediated by CRISPR/Cas9 systems is due to become a beneficial therapeutic option for treating genetic diseases and some cancers. However, there are challenges in delivering CRISPR components which necessitate sophisticated delivery systems for safe and effective genome editing. Lipid nanoparticles (LNPs) have become an attractive nonviral delivery platform for CRISPR-mediated genome editing due to their low immunogenicity and application flexibility. In this review, we provide a background of CRISPR-mediated gene therapy, as well as LNPs and their applicable characteristics for delivering CRISPR components. We then highlight the challenges of CRISPR delivery, which have driven the significant development of new, safe, and optimized LNP formulations in the past decade. Finally, we discuss considerations for using LNPs to deliver CRISPR and future perspectives on clinical translation of LNP-CRISPR gene editing.

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主要研究问题 ​

  1. 在使用脂质纳米颗粒（LNP）传递CRISPR/Cas9组件时，如何评估其在不同细胞类型中的有效性和安全性？
  2. 目前有哪些新兴的LNP配方被开发用于提高CRISPR组件的传递效率？
  3. CRISPR/Cas9基因编辑在治疗特定遗传疾病中的应用前景如何，特别是与LNP结合使用时？
  4. 除了LNP，是否有其他非病毒载体在CRISPR组件传递中显示出潜力，具体表现如何？
  5. 在临床转化过程中，LNP与CRISPR技术结合所面临的主要伦理和监管挑战是什么？

核心洞察 ​

研究背景和目的 ​

CRISPR/Cas9基因编辑技术因其能够精准修复基因突变而备受关注，尤其在遗传疾病和某些癌症的治疗中展现出巨大潜力。然而，CRISPR组件的有效递送面临诸多挑战，因此需要开发安全有效的递送系统。脂质纳米颗粒（LNPs）作为一种非病毒递送平台，因其低免疫原性和应用灵活性而成为理想选择。本综述旨在探讨LNP在CRISPR/Cas9基因编辑中的应用，包括其组成、优缺点及未来发展方向。

主要方法/材料/实验设计 ​

本研究采用文献综述的方式，综合分析了LNP的组成、作用机制及其在CRISPR/Cas9递送中的应用。

Mermaid diagram

关键结果和发现 ​

  1. LNP组成：LNP主要由四种成分构成：离子型阳离子脂质、PEG脂质、两性磷脂和胆固醇。离子型阳离子脂质显著提高了核酸的包封和递送效率。
  2. 递送方式：LNP可以递送不同形式的CRISPR组件，包括质粒DNA、mRNA和RNP复合物。每种形式的递送都有其独特的优缺点。
  3. 临床试验：LNP作为CRISPR/Cas9递送平台的临床应用逐渐展开，Intellia Therapeutics已启动针对遗传性淀粉样变病的临床试验。

主要结论/意义/创新性 ​

LNP为CRISPR/Cas9基因编辑提供了一种安全、高效的递送手段。其优越的生物相容性和针对性使其在基因治疗领域展现出广泛的应用前景。未来的研究将聚焦于优化LNP的组成和结构，以提高其递送效率和靶向特异性。

研究局限性和未来方向 ​

尽管LNP在基因递送中表现出色，但仍存在以下局限性：

  • 递送效率：不同细胞类型对LNP的摄取能力不同，需优化LNP的表面修饰以提高特异性。
  • 免疫反应：尽管LNP的免疫原性较低，但仍需评估其在体内的长期安全性。
  • 递送模板：在HDR修复中，需同时递送额外的DNA模板，这增加了递送的复杂性。

未来的研究应集中在开发更具靶向性的LNP系统，以及探索其在其他疾病治疗中的潜力。

参考文献 ​

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引用本文的文献 ​

  1. The promise of gene editing: so close and yet so perilously far. - David J Segal - Frontiers in genome editing (2022)
  2. Nanocarriers: A novel strategy for the delivery of CRISPR/Cas systems. - Faranak Hejabi;Mohammad Sadegh Abbaszadeh;Shirinsadat Taji;Andrew O'Neill;Fatemeh Farjadian;Mohammad Doroudian - Frontiers in chemistry (2022)
  3. Delivery of RNAs to Specific Organs by Lipid Nanoparticles for Gene Therapy. - Kelly Godbout;Jacques P Tremblay - Pharmaceutics (2022)
  4. In vivo delivery of CRISPR-Cas9 genome editing components for therapeutic applications. - Kun Huang;Daniel Zapata;Yan Tang;Yong Teng;Yamin Li - Biomaterials (2022)
  5. Lipid-mRNA nanoparticles landscape for cancer therapy. - Yin Li;Hengtong Fang;Tao Zhang;Yu Wang;Tingting Qi;Bai Li;Huping Jiao - Frontiers in bioengineering and biotechnology (2022)
  6. Advanced Nanomedicine for High-Risk HPV-Driven Head and Neck Cancer. - Qiang Xu;Ye Chen;Yuan Jin;Zhiyu Wang;Haoru Dong;Andreas M Kaufmann;Andreas E Albers;Xu Qian - Viruses (2022)
  7. Shaping the future from the small scale: dry powder inhalation of CRISPR-Cas9 lipid nanoparticles for the treatment of lung diseases. - Simone P Carneiro;Antonietta Greco;Enrica Chiesa;Ida Genta;Olivia M Merkel - Expert opinion on drug delivery (2023)
  8. Recent advances in the delivery and applications of nonviral CRISPR/Cas9 gene editing. - Frazer Sinclair;Anjuman A Begum;Charles C Dai;Istvan Toth;Peter M Moyle - Drug delivery and translational research (2023)
  9. Spatial Transcriptomics: Technical Aspects of Recent Developments and Their Applications in Neuroscience and Cancer Research. - Han-Eol Park;Song Hyun Jo;Rosalind H Lee;Christian P Macks;Taeyun Ku;Jihwan Park;Chung Whan Lee;Junho K Hur;Chang Ho Sohn - Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2023)
  10. Recent Advances in Site-Specific Lipid Nanoparticles for mRNA Delivery. - Xiao Xu;Tian Xia - ACS nanoscience Au (2023)

... (72 更多 篇文献)

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