Gene Regulation Using Spherical Nucleic Acids to Treat Skin Disorders.
Gene Regulation Using Spherical Nucleic Acids to Treat Skin Disorders.
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DOI：
10.3390/ph13110360
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发表时间：
2020-11-02
期刊：
影响因子：
--
通讯作者：
Paller AS
中科院分区：
文献类型：
--
作者：
Holmes TR;Paller AS
球形核酸（SNA）是由呈球形构型的核酸组成的纳米结构，通常围绕纳米颗粒核心。与常规基因治疗相比，SNA作为基因调节剂是有利的，这是由于它们的低毒性、增强的稳定性、被几乎任何细胞摄取以及穿透表皮屏障的能力。在这次审查中，我们：（i）描述SNA的产生、结构和性质;（ii）详细说明SNA在角质形成细胞中的摄取机制，由清道夫受体调节;（iii）报告SNA如何局部应用和病灶内注射治疗皮肤病。被称为nanoflares的专门SNA可以局部应用于基于基因的诊断（疤痕与正常组织）。针对TNFα和白细胞介素-17A受体的局部SNA在小鼠模型中逆转了银屑病样疾病，并已在I期人体试验中进行了测试。此外，靶向神经节苷脂GM 3合酶的SNA加速糖尿病小鼠模型中的伤口愈合。最近，靶向toll样受体9的SNA正在通过肿瘤内注射用于2期人体试验，以诱导默克尔细胞和皮肤鳞状细胞癌中的免疫应答。总的来说，SNA是台式和临床研究中的有价值的工具，并且它们的有利特性，包括在局部递送后渗透到表皮中，为靶向治疗提供了新的机会。
Spherical nucleic acids (SNAs) are nanostructures consisting of nucleic acids in a spherical configuration, often around a nanoparticle core. SNAs are advantageous as gene-regulating agents compared to conventional gene therapy owing to their low toxicity, enhanced stability, uptake by virtually any cell, and ability to penetrate the epidermal barrier. In this review we: (i) describe the production, structure and properties of SNAs; (ii) detail the mechanism of SNA uptake in keratinocytes, regulated by scavenger receptors; and (iii) report how SNAs have been topically applied and intralesionally injected for skin disorders. Specialized SNAs called nanoflares can be topically applied for gene-based diagnosis (scar vs. normal tissue). Topical SNAs directed against TNFα and interleukin-17A receptor reversed psoriasis-like disease in mouse models and have been tested in Phase 1 human trials. Furthermore, SNAs targeting ganglioside GM3 synthase accelerate wound healing in diabetic mouse models. Most recently, SNAs targeting toll-like receptor 9 are being used in Phase 2 human trials via intratumoral injection to induce immune responses in Merkel cell and cutaneous squamous cell carcinoma. Overall, SNAs are a valuable tool in bench-top and clinical research, and their advantageous properties, including penetration into the epidermis after topical delivery, provide new opportunities for targeted therapies.
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DOI：
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发表时间：
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影响因子：
11.1
作者：
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通讯作者：
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DOI：
10.1073/pnas.2005794117
发表时间：
2020-07-28
影响因子：
11.1
作者：
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通讯作者：
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