Although antisense oligomers (ASOs) have been successfully utilized to control gene expression, they have been little exploited to control Candida albicans virulence's determinants. Filamentation is an important virulence factor of C. albicans, and RAS1 and RIM101 genes are involved in its regulation. Thus, the main goal of this work was to project ASOs, based on 2'-OMethyl chemical modification, to target RAS1 and RIM101 mRNA and to validate its application either alone or in combination, to reduce Candida filamentation in different human body fluids. It was verified that both, anti-RAS1 2'OMe and anti-RIM101 2'OMe oligomers, were able to reduce the levels of RAS1 and RIM101 genes’ expression and to significantly reduce C. albicans filamentation. Furthermore, the combined application of anti-RAS1 2'OMe oligomer and anti-RIM101 2'OMe oligomer enhances the control of C. albicans filamentation in artificial saliva and urine. Our work confirms that ASOs are useful tools for research and therapeutic development on the control of candidiasis.

中文翻译：

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抗 RAS1 和抗 RIM101 2'-O甲基RNA 寡聚体的联合应用增强了白色念珠菌丝状体的控制

尽管反义寡聚体 (ASO) 已成功用于控制基因表达，但很少有人利用它们来控制白色念珠菌毒力的决定因素。丝状化是白色念珠菌的重要毒力因子，RAS1和RIM101基因参与其调控。因此，这项工作的主要目标是设计基于 2'-O 甲基化学修饰的 ASO，以靶向 RAS1 和 RIM101 mRNA，并验证其单独或组合的应用，以减少不同人体体液中的念珠菌丝状体。经证实，抗 RAS1 2'OMe 和抗 RIM101 2'OMe 寡聚体都能够降低 RAS1 和 RIM101 基因的表达水平并显着降低白色念珠菌丝状体。此外，抗RAS1 2'的联合应用 OMe 寡聚体和抗 RIM101 2'OMe 寡聚体增强了对人工唾液和尿液中白色念珠菌丝状体的控制。我们的工作证实 ASO 是控制念珠菌病的研究和治疗开发的有用工具。