用于基因治疗的脂质纳米颗粒表面修饰。

IF 3.2 4区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Belal Tafech, Fatemeh Mohabatpour, Sarah Hedtrich
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引用次数: 0

摘要

基因疗法具有靶向和有效治疗多种疾病的潜力,包括癌症以及遗传、神经和自身免疫性疾病。尽管我们在确定传递遗传货物的非病毒策略方面取得了重大进展,但仍存在某些局限性。一般来说,基因传递具有挑战性的原因有几个,包括核酸对酶和化学降解的不稳定性以及限制性生物屏障(如细胞、内体和核膜)的存在。脂质纳米颗粒(LNPs)的出现帮助克服了许多这些挑战。尽管取得了成功,但LNPs需要进一步优化才能有效地将基因传递到肝外组织,因为LNPs在全身给药后有利于在肝脏中积累。在这篇小型综述中,我们概述了目前的临床前方法,其中LNP表面修饰通过偶联适配体、抗体和肽等来利用细胞和组织靶向。除了它们的细胞摄取和提高效率的作用,我们概述了不同的靶向部分和常用的偶联策略的(缺点)优势。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Surface modification of lipid nanoparticles for gene therapy

Surface modification of lipid nanoparticles for gene therapy

Surface modification of lipid nanoparticles for gene therapy

Gene therapies have the potential to target and effectively treat a variety of diseases including cancer as well as genetic, neurological, and autoimmune disorders. Although we have made significant advances in identifying non-viral strategies to deliver genetic cargo, certain limitations remain. In general, gene delivery is challenging for several reasons including the instabilities of nucleic acids to enzymatic and chemical degradation and the presence of restrictive biological barriers such as cell, endosomal and nuclear membranes. The emergence of lipid nanoparticles (LNPs) helped overcome many of these challenges. Despite its success, further optimization is required for LNPs to yield efficient gene delivery to extrahepatic tissues, as LNPs favor accumulation in the liver after systemic administration. In this mini-review, we provide an overview of current preclinical approaches in that LNP surface modification was leveraged for cell and tissue targeting by conjugating aptamers, antibodies, and peptides among others. In addition to their cell uptake and efficiency-enhancing effects, we outline the (dis-)advantages of the different targeting moieties and commonly used conjugation strategies.

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来源期刊
Journal of Gene Medicine
Journal of Gene Medicine 医学-生物工程与应用微生物
CiteScore
6.40
自引率
0.00%
发文量
80
审稿时长
6-12 weeks
期刊介绍: The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.
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