Exosomes as an Emerging Plasmid Delivery Vehicle for Gene Therapy.
Exosomes as an Emerging Plasmid Delivery Vehicle for Gene Therapy.
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DOI：
10.3390/pharmaceutics15071832
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发表时间：
2023-06-27
期刊：
影响因子：
5.4
通讯作者：
中科院分区：
文献类型：
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作者：
尽管基因疗法在三十多年前就已推出，但它在治疗多种疾病方面尚未达到预期的潜力，并且仍然缺乏广泛的临床应用。这种治疗方式临床可转化性的根本限制一直是有效的递送系统，该系统避免了治疗性核酸的降解，确保它们到达预期的疾病目标。用于引入外源基因的质粒 DNA (pDNA) 由于其大小和潜在的免疫原性而提出了额外的挑战。目前的 pDNA 方法包括裸露的 pDNA 结合电穿孔或超声、脂质体、其他纳米颗粒和细胞穿透肽等。虽然有大量评论的主题，但这些方法中的每一种都有其独特的局限性、副作用和功效问题。在这篇综述中，我们重点介绍了外泌体在基因治疗中递送 pDNA 的新兴用途。我们特别关注牛乳和初乳衍生的外泌体作为纳米递送“平台”。牛奶/初乳代表了一种丰富、可扩展且具有成本效益的外泌体天然来源，可以装载核酸以靶向递送至体内的多种组织类型。这些纳米粒子可以进行功能化并装载 pDNA，用于基因的外源表达，以针对多种疾病表型，克服当前基因治疗递送技术的许多限制。
Despite its introduction more than three decades ago, gene therapy has fallen short of its expected potential for the treatment of a broad spectrum of diseases and continues to lack widespread clinical use. The fundamental limitation in clinical translatability of this therapeutic modality has always been an effective delivery system that circumvents degradation of the therapeutic nucleic acids, ensuring they reach the intended disease target. Plasmid DNA (pDNA) for the purpose of introducing exogenous genes presents an additional challenge due to its size and potential immunogenicity. Current pDNA methods include naked pDNA accompanied by electroporation or ultrasound, liposomes, other nanoparticles, and cell-penetrating peptides, to name a few. While the topic of numerous reviews, each of these methods has its own unique set of limitations, side effects, and efficacy concerns. In this review, we highlight emerging uses of exosomes for the delivery of pDNA for gene therapy. We specifically focus on bovine milk and colostrum-derived exosomes as a nano-delivery “platform”. Milk/colostrum represents an abundant, scalable, and cost-effective natural source of exosomes that can be loaded with nucleic acids for targeted delivery to a variety of tissue types in the body. These nanoparticles can be functionalized and loaded with pDNA for the exogenous expression of genes to target a wide variety of disease phenotypes, overcoming many of the limitations of current gene therapy delivery techniques.
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影响因子：
5.7
作者：
Alhakamy NA;Ishiguro S;Uppalapati D;Berkland CJ;Tamura M
通讯作者：
Tamura M
DOI：
10.1016/j.nano.2017.03.001
发表时间：
2017-07-01
影响因子：
5.4
作者：
Agrawal, Ashish K.;Aqil, Farrukh;Gupta, Ramesh C.
通讯作者：
Gupta, Ramesh C.
DOI：
10.20517/evcna.2020.09
发表时间：
2021
期刊：
Extracellular vesicles and circulating nucleic acids
影响因子：
--
作者：
Comfort N;Bloomquist TR;Shephard AP;Petty CR;Cunningham A;Hauptman M;Phipatanakul W;Baccarelli A
通讯作者：
Baccarelli A
影响因子：
1.4
作者：
Al-Zahrani, Samiyah Saeed;Bora, Roop Singh;Al-Garni, Saleh Mohammed
通讯作者：
Al-Garni, Saleh Mohammed
影响因子：
4.1
作者：
Chopra, Neha;Arya, Braham Dutt;Choudhury, Sangeeta
通讯作者：
Choudhury, Sangeeta