KAIST

Candida, a type of fungus, which can spread throughout the body via the bloodstream, leading to organ damage and sepsis. Recently, the incidence of candidiasis has surged due to the increase in immunosuppressive therapies, medical implants, and transplantation. Korean researchers have successfully developed a next-generation treatment that, unlike existing antifungals, selectively acts only on Candida, achieving both high therapeutic efficacy and low side effects simultaneously.

KAIST (President Kwang Hyung Lee) announced on the 8th that a research team led by Professor Hyun-Jung Chung of the Department of Biological Sciences, in collaboration with Professor Yong Pil Jeong's team at Asan Medical Center, developed a gene-based nanotherapy (FTNx) that simultaneously inhibits two key enzymes in the Candida cell wall.

Current antifungal drugs for Candida have low target selectivity, which can affect human cells. Furthermore, their therapeutic efficacy is gradually decreasing due to the emergence of new resistant strains. Especially for immunocompromised patients, the infection progresses rapidly and has a poor prognosis, making the development of new treatments to overcome the limitations of existing therapies urgent.

The developed treatment can be administered systemically, and by combining gene suppression technology with nanomaterial technology, it effectively overcomes the structural limitations of existing compound-based drugs and successfully achieves selective treatment against only Candida.

The research team created a gold nanoparticle-based complex loaded with short DNA fragments called antisense oligonucleotides (ASO), which simultaneously target two crucial enzymes—β-1,3-glucan synthase (FKS1) and chitin synthase (CHS3)—important for forming the cell wall of the Candida fungus.

By applying a surface coating technology that binds to a specific glycolipid structure (a structure combining sugar and fat) on the Candida cell wall, a targeted delivery device was implemented. This successfully achieved a precise targeting effect, ensuring the complex is not delivered to human cells at all but acts selectively only on Candida.

<Figure 1: Overview of antifungal therapy design and experimental approach>

This complex, after entering Candida cells, cleaves the mRNA produced by the FKS1 and CHS3 genes, thereby inhibiting translation and simultaneously blocking the synthesis of cell wall components β-1,3-glucan and chitin. As a result, the

Candida cell wall loses its structural stability and collapses, suppressing bacterial survival and proliferation.

In fact, experiments using a systemic candidiasis model in mice confirmed the therapeutic effect: a significant reduction in

Candida count in the organs, normalization of immune responses, and a notable increase in survival rates were observed in the treated group.

Professor Hyun-Jung Chung, who led the research, stated, "This study presents a method to overcome the issues of human toxicity and drug resistance spread with existing treatments, marking an important turning point by demonstrating the applicability of gene therapy for systemic infections". She added, "We plan to continue research on optimizing administration methods and verifying toxicity for future clinical application."

This research involved Ju Yeon Chung and Yoon-Kyoung Hong as co-first authors , and was published in the international journal 'Nature Communications' on July 1st.

• Paper Title: Effective treatment of systemic candidiasis by synergistic targeting of cell wall synthesis
• DOI: 10.1038/s41467-025-60684-7
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This research was supported by the Ministry of Health and Welfare and the National Research Foundation of Korea.