Mohammadian Farsani Arezoo, Mokhtari Negin, Nooraei Saghi, Bahrulolum Howra, Akbari Ali, Farsani Zoheir Mohammadian, Khatami Seyedmoein, Ebadi Mozhdeh Sadat, Ahmadian Gholamreza
Department of Industrial and Environmental Biotechnology, National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi Univesity, Tehran, Iran.
Heliyon. 2024 Jan 11;10(2):e24606. doi: 10.1016/j.heliyon.2024.e24606. eCollection 2024 Jan 30.
The steady progress in genome editing, especially genome editing based on the use of clustered regularly interspaced short palindromic repeats (CRISPR) and programmable nucleases to make precise modifications to genetic material, has provided enormous opportunities to advance biomedical research and promote human health. However, limited transfection efficiency of CRISPR-Cas9 poses a substantial challenge, hindering its wide adoption for genetic modification. Recent advancements in nanoparticle technology, specifically lipid nanoparticles (LNPs), offer promising opportunities for targeted drug delivery. LNPs are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. Notably, certain LNPs, such as Polyethylene glycol-phospholipid-modified cationic lipid nanoparticles and solid lipid nanoparticles, exhibit remarkable potential for efficient CRISPR-Cas9 delivery as a gene editing instrument. This review will introduce the molecular mechanisms and diverse applications of the CRISPR/Cas9 gene editing system, current strategies for delivering CRISPR/Cas9-based tools, the advantage of LNPs for CRISPR-Cas9 delivery, an overview of strategies for overcoming off-target genome editing, and approaches for improving genome targeting and tissue targeting. We will also highlight current developments and recent clinical trials for the delivery of CRISPR/Cas9. Finally, future directions for overcoming the limitations and adaptation of this technology for clinical trials will be discussed.
基因组编辑技术不断取得稳步进展，特别是基于成簇规律间隔短回文重复序列（CRISPR）和可编程核酸酶对遗传物质进行精确修饰的基因组编辑技术，为推动生物医学研究和促进人类健康提供了巨大机遇。然而，CRISPR-Cas9有限的转染效率构成了重大挑战，阻碍了其在基因编辑中的广泛应用。纳米颗粒技术的最新进展，特别是脂质纳米颗粒（LNPs），为靶向药物递送提供了有前景的机会。LNPs作为一种递送治疗药物的手段正变得越来越流行，包括基于核酸和mRNA的药物。值得注意的是，某些LNPs，如聚乙二醇-磷脂修饰的阳离子脂质纳米颗粒和固体脂质纳米颗粒，作为一种基因编辑工具，在高效递送CRISPR-Cas9方面具有显著潜力。本综述将介绍CRISPR/Cas9基因编辑系统的分子机制和多样应用、目前递送基于CRISPR/Cas9工具的策略、LNPs用于递送CRISPR-Cas9的优势、克服脱靶基因组编辑的策略概述以及改善基因组靶向和组织靶向的方法。我们还将重点介绍目前CRISPR/Cas9递送的发展情况和近期临床试验。最后，将讨论克服该技术局限性以及使其适用于临床试验的未来方向。
