用于RNA递送的生物启发脂质纳米载体

IF 3.8 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY ACS Bio & Med Chem Au Pub Date : 2023-01-16 DOI:10.1021/acsbiomedchemau.2c00073
Alex Golubovic, Shannon Tsai and Bowen Li*, 
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引用次数: 3

摘要

RNA治疗是一项颠覆性技术,包括一类快速扩展的药物。将RNA疗法进一步转化为临床将改善许多疾病的治疗,并有助于实现个性化医疗。然而,由于缺乏合适的递送工具,RNA的体内递送仍然具有挑战性。目前最先进的载体,如可电离的脂质纳米颗粒,仍然面临着重大挑战,包括频繁定位于清除相关器官和有限的(1-2%)内体逃逸。因此,必须改进递送载体,以进一步释放RNA疗法的全部潜力。一种新兴的策略是通过结合仿生设计原理来修饰现有或新的脂质纳米载体。这种方法通常旨在改善组织靶向、细胞摄取和内体逃逸,解决该领域面临的一些关键问题。在这篇综述中,我们介绍了创建基于生物启发的脂质的RNA载体的不同策略,并根据报道的结果讨论了每种策略的潜在含义。这些策略包括将天然衍生的脂质结合到现有的纳米载体中,并模仿生物衍生的分子、病毒和外泌体。我们根据交付车辆成功所需的关键因素来评估每种策略。最后,我们指出了需要进一步研究的领域,以便能够更成功地合理设计用于RNA递送的脂质纳米载体。
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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Bioinspired Lipid Nanocarriers for RNA Delivery

RNA therapy is a disruptive technology comprising a rapidly expanding category of drugs. Further translation of RNA therapies to the clinic will improve the treatment of many diseases and help enable personalized medicine. However, in vivo delivery of RNA remains challenging due to the lack of appropriate delivery tools. Current state-of-the-art carriers such as ionizable lipid nanoparticles still face significant challenges, including frequent localization to clearance-associated organs and limited (1–2%) endosomal escape. Thus, delivery vehicles must be improved to further unlock the full potential of RNA therapeutics. An emerging strategy is to modify existing or new lipid nanocarriers by incorporating bioinspired design principles. This method generally aims to improve tissue targeting, cellular uptake, and endosomal escape, addressing some of the critical issues facing the field. In this review, we introduce the different strategies for creating bioinspired lipid-based RNA carriers and discuss the potential implications of each strategy based on reported findings. These strategies include incorporating naturally derived lipids into existing nanocarriers and mimicking bioderived molecules, viruses, and exosomes. We evaluate each strategy based on the critical factors required for delivery vehicles to succeed. Finally, we point to areas of research that should be furthered to enable the more successful rational design of lipid nanocarriers for RNA delivery.

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来源期刊
ACS Bio & Med Chem Au
ACS Bio & Med Chem Au 药物、生物、化学-
CiteScore
4.10
自引率
0.00%
发文量
0
期刊介绍: ACS Bio & Med Chem Au is a broad scope open access journal which publishes short letters comprehensive articles reviews and perspectives in all aspects of biological and medicinal chemistry. Studies providing fundamental insights or describing novel syntheses as well as clinical or other applications-based work are welcomed.This broad scope includes experimental and theoretical studies on the chemical physical mechanistic and/or structural basis of biological or cell function in all domains of life. It encompasses the fields of chemical biology synthetic biology disease biology cell biology agriculture and food natural products research nucleic acid biology neuroscience structural biology and biophysics.The journal publishes studies that pertain to a broad range of medicinal chemistry including compound design and optimization biological evaluation molecular mechanistic understanding of drug delivery and drug delivery systems imaging agents and pharmacology and translational science of both small and large bioactive molecules. Novel computational cheminformatics and structural studies for the identification (or structure-activity relationship analysis) of bioactive molecules ligands and their targets are also welcome. The journal will consider computational studies applying established computational methods but only in combination with novel and original experimental data (e.g. in cases where new compounds have been designed and tested).Also included in the scope of the journal are articles relating to infectious diseases research on pathogens host-pathogen interactions therapeutics diagnostics vaccines drug-delivery systems and other biomedical technology development pertaining to infectious diseases.
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