Saccharomyces cerevisiae (Baker’s Yeast) as an Interfering RNA Expression and Delivery System

Duman-Scheel, Molly

doi:10.2174/1389450120666181126123538

Cited by 47 publications

(77 citation statements)

References 78 publications

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“…The development of encapsulated stable formulations that promote IRP stability in various environmental conditions, both prior to and during use, will also be critical. Encapsulation could also facilitate controlled and extended release of IRPs, promoting increased residual activity [10]. The results of this investigation indicate that investing in these endeavors could significantly advance mosquito control efforts.…”

Section: Discussionmentioning

confidence: 88%

“…In recent studies, we have engineered S. cerevisiae to express shRNAs corresponding to larvicidal siRNAs identified in larval lethality screens [5][6][7][8]10]. Yeast cultured from these strains can be heat-inactivated and dried into a tablet formulation that can be used as a larvicide [5].…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

“…To initiate these studies, we pursued screens that led to the identification of siRNAs that target genes required for mosquito larval viability [5][6][7][8]. Following discovery of these siRNAs, S. cerevisiae (baker's yeast) was bioengineered to express shRNAs corresponding to the larvicidal siRNAs, creating a yeast expression and delivery system for larvicidal IRPs [5,9,10]. Subsequent work has prioritized characterization of yeast IRPs with target sites that are conserved in multiple species of disease vector mosquitoes.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of a dual-action adulticidal and larvicidal interfering RNA pesticide targeting the Shaker gene of multiple disease vector mosquitoes

et al. 2020

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The existing mosquito pesticide repertoire faces great challenges to sustainability, and new classes of pesticides are vitally needed to address established and emerging mosquitoborne infectious diseases. RNA interference-(RNAi-) based pesticides are emerging as a promising new biorational mosquito control strategy. In this investigation, we describe characterization of an interfering RNA pesticide (IRP) corresponding to the mosquito Shaker (Sh) gene, which encodes an evolutionarily conserved voltage-gated potassium channel subunit. Delivery of the IRP to Aedes aegypti adult mosquitoes in the form of siRNA that was injected or provided as an attractive toxic sugar bait (ATSB) led to Sh gene silencing that resulted in severe neural and behavioral defects and high levels of adult mortality. Likewise, when provided to A. aegypti larvae in the form of short hairpin RNA (shRNA) expressed in Saccharomyces cerevisiae (baker's yeast) that had been formulated into a dried inactivated yeast tablet, the yeast IRP induced neural defects and larval death. Although the Sh IRP lacks a known target site in humans or other non-target organisms, conservation of the target site in the Sh genes of multiple mosquito species suggested that it may function as a biorational broad-range mosquito insecticide. In support of this, the Sh IRP induced both adult and larval mortality in treated Aedes albopictus, Anopheles gambiae, and Culex quinquefasciatus mosquitoes, but was not toxic to non-target arthropods. These studies indicated that IRPs targeting Sh could one day be used in integrated biorational mosquito control programs for the prevention of multiple mosquito-borne illnesses. The results of this investigation also suggest that the species-specificity of ATSB technology, a new paradigm for vector control, could be enhanced through the use of RNAi-based pesticides.

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Section: Discussionmentioning

confidence: 88%

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characterization of a dual-action adulticidal and larvicidal interfering RNA pesticide targeting the Shaker gene of multiple disease vector mosquitoes

et al. 2020

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“…Broad use of these larvicides for mosquito control requires the identification of effective, affordable, and stakeholder-accepted means of introducing the RNAi larvicides to mosquito control programs worldwide. Evaluation of multiple interfering RNA delivery mechanisms in the laboratory resulted in the identification of baker's yeast (Saccharomyces cerevisiae) as a promising RNA expression and delivery system [18].…”

Section: Introductionmentioning

confidence: 99%

Community acceptance of yeast interfering RNA larvicide technology for control of Aedes mosquitoes in Trinidad

et al. 2020

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RNA interference (RNAi), a technique used to investigate gene function in insects and other organisms, is attracting attention as a potential new technology for mosquito control. Saccharomyces cerevisiae (baker's yeast) was recently engineered to produce interfering RNA molecules that silence genes required for mosquito survival, but which do not correspond to genes in humans or other non-target organisms. The resulting yeast pesticides, which facilitate cost-effective production and delivery of interfering RNA to mosquito larvae that eat the yeast, effectively kill mosquitoes in laboratory and semi-field trials. In preparation for field evaluation of larvicides in Trinidad, a Caribbean island with endemic diseases resulting from pathogens transmitted by Aedes mosquitoes, adult residents living in the prospective trial site communities of Curepe, St. Augustine, and Tamana were engaged. Open community forums and paper surveys were used to assess the potential acceptability, societal desirability, and sustainability of yeast interfering RNA larvicides. These assessments revealed that Trinidadians have good working knowledge of mosquitoes and mosquito-borne illnesses. A majority of the respondents practiced some method of larval mosquito control and agreed that they would use a new larvicide if it were proven to be safe and effective. During the community engagement forums, participants were educated about mosquito biology, mosquitoborne diseases, and the new yeast larvicides. When invited to provide feedback, engagement forum attendees were strongly supportive of the new technology, raised few concerns, and provided helpful advice regarding optimal larvicide formulations, insecticide application, operational approaches for using the larvicides, and pricing. The results of these studies suggest that the participants are supportive of the potential use of yeast interfering RNA larvicides in Trinidad and that the communities assessed in this investigation represent viable field sites.

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“…This difference affects the structure, properties, and possibly the activity and immunogenicity of these molecules (reviewed in Yu et al, 2019). Also, effort has been made to bioengineer RNA molecules in living cells, including in bacteria and yeast (Huang et al, 2013;Chen et al, 2015;Pereira et al, 2017b;Ho et al, 2018;Kaur et al, 2018;Duman-Scheel, 2019). These bioengineered RNA agents (BERA) can be produced in large scale and carry no or minimal posttranscriptional modifications (Li et al, 2015;Wang et al, 2015).…”

Section: Berasmentioning

confidence: 99%

Transcription and Translation Inhibitors in Cancer Treatment

et al. 2020

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Transcription and translation are fundamental cellular processes that govern the protein production of cells. These processes are generally up regulated in cancer cells, to maintain the enhanced metabolism and proliferative state of these cells. As such cancerous cells can be susceptible to transcription and translation inhibitors. There are numerous druggable proteins involved in transcription and translation which make lucrative targets for cancer drug development. In addition to proteins, recent years have shown that the "undruggable" transcription factors and RNA molecules can also be targeted to hamper the transcription or translation in cancer. In this review, we summarize the properties and function of the transcription and translation inhibitors that have been tested and developed, focusing on the advances of the last 5 years. To complement this, we also discuss some of the recent advances in targeting oncogenes tightly controlling transcription including transcription factors and KRAS. In addition to natural and synthetic compounds, we review DNA and RNA based approaches to develop cancer drugs. Finally, we conclude with the outlook to the future of the development of transcription and translation inhibitors.

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Saccharomyces cerevisiae (Baker’s Yeast) as an Interfering RNA Expression and Delivery System

Cited by 47 publications

References 78 publications

Characterization of a dual-action adulticidal and larvicidal interfering RNA pesticide targeting the Shaker gene of multiple disease vector mosquitoes

Characterization of a dual-action adulticidal and larvicidal interfering RNA pesticide targeting the Shaker gene of multiple disease vector mosquitoes

Community acceptance of yeast interfering RNA larvicide technology for control of Aedes mosquitoes in Trinidad

Transcription and Translation Inhibitors in Cancer Treatment

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