Delivery of therapeutic RNA by extracellular vesicles derived from Saccharomyces cerevisiae for medicine applications

J Pharm Sci. 2024 Dec;113(12):3574-3585. doi: 10.1016/j.xphs.2024.10.035. Epub 2024 Oct 23.

Abstract

Employing small extracellular vesicles (EVs) as drug delivery vehicles presents a plethora of advantages over conventional drug delivery methods, including biological compatibility, engineering versatility for targeted delivery, and biodegradability. Therefore, strategies aimed at amplifying their therapeutic potential involve developing efficient, tissue-specific, and non-immunogenic delivery approaches. Despite rapid advancements in the realm of EVs as drug delivery systems in recent years, the availability of a high-yield, reproducible, and cost-effective source for EVs production and isolation remains a limiting factor for practical application. In this study, we isolated EVs from Saccharomyces cerevisiae (S.c) and loaded them with cargoes such as hsa-miR-143 (an apoptosis-inducing miRNA) or miR-H6 (a miRNA targeting HSV-1). We demonstrated the capability of these EVs to deliver microRNAs or even large mRNA to a variety of cell types. The therapeutic potential of S.c-derived EVs (S.c-EVs) was further evidenced by their ability to inhibit tumor growth in animal models. The S.c-EVs proved to be safe and non-immunogenic in vivo. Our results suggest that Saccharomyces cerevisiae represents a cost-effective source of extracellular vesicles, serving as nanocarriers for functional drug delivery in therapeutic applications.

Keywords: Delivery; Extracellular vesicles (EVs); RNA; Saccharomyces cerevisiae (S.c).

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Drug Delivery Systems* / methods
  • Extracellular Vesicles* / metabolism
  • Humans
  • Mice
  • MicroRNAs* / administration & dosage
  • MicroRNAs* / genetics
  • Saccharomyces cerevisiae* / genetics

Substances

  • MicroRNAs