Abstract
The broad application of RNA interference for disease prevention is dependent upon the production of dsRNA in an economically feasible, scalable, and sustainable fashion, as well as the identification of safe and effective methods for RNA delivery. Current research has sparked interest in the use of Saccharomyces cerevisiae for these applications. This review examines the potential for commercial development of yeast interfering RNA expression and delivery systems. S. cerevisiae is a genetic model organism that lacks a functional RNA interference system, which may make it an ideal system for expression and accumulation of high levels of recombinant interfering RNA. Moreover, recent studies in a variety of eukaryotic species suggest that this microbe may be an excellent and safe system for interfering RNA delivery. Key areas for further research and development include optimization of interfering RNA expression in S. cerevisiae, industrial-sized scaling of recombinant yeast cultures in which interfering RNA molecules are expressed, the development of methods for large-scale drying of yeast that preserve interfering RNA integrity, and identification of encapsulating agents that promote yeast stability in various environmental conditions. The genetic tractability of S. cerevisiae and a long history of using this microbe in both the food and pharmaceutical industry will facilitate further development of this promising new technology, which has many potential applications of medical importance.
Highlights
Saccharomyces cerevisiae, known as baker’s or budding yeast, is a non-infectious microbe and genetic model organism
A deficiency of functional RNA interference (RNAi) machinery in S. cerevisiae, which lacks both Dicer and Argonaute [3], may have initially caused it to be overlooked as a system for producing interfering RNA molecules
S. cerevisiase has been investigated as a potential vaccine carrier, as its complex cell wall components and appropriate size facilitate the specific uptake of this microbe by Dendritic Cells (DCs) [22], professional antigen-presenting cells that function in innate and adaptive immune responses [2325]
Summary
Saccharomyces cerevisiae, known as baker’s or budding yeast, is a non-infectious microbe and genetic model organism. Key advancements resulting from the generation of yeast strains expressing recombinant interfering RNA molecules are noted here and discussed in further detail in this review. A deficiency of functional RNAi machinery in S. cerevisiae, which lacks both Dicer and Argonaute [3], may have initially caused it to be overlooked as a system for producing interfering RNA molecules This lack of RNAi machinery may, promote the accumulation of bioengineered dsRNAs in yeasts, making it an ideal system for RNA production. Expression of dsRNA in chloroplasts led to accumulation of dsRNA at high levels, up to 0.4% of total cellular RNA These findings, which have generated interest in using the chloroplast genome to express dsRNAs targeting crop pests [18], may be applicable to yeast dsRNA expression systems. In addition to discussing potential applications, this review summarizes requisite research and development that will facilitate the commercialization of this technology
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