4.7 Review

Exosomes as an Emerging Plasmid Delivery Vehicle for Gene Therapy

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PHARMACEUTICS
卷 15, 期 7, 页码 -

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MDPI
DOI: 10.3390/pharmaceutics15071832

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exosomes; nanoplatform; plasmid DNA delivery; cancer; gene therapy

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Despite its introduction more than three decades ago, gene therapy has not lived up to its potential due to the lack of an effective delivery system. This review highlights the use of exosomes derived from bovine milk and colostrum as a nano-delivery platform for gene therapy. These exosomes provide an abundant, scalable, and cost-effective source for targeted delivery of nucleic acids, overcoming the limitations of current gene therapy delivery techniques.
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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