"Genes Switched Off Only When Desired"... IBS Expands Vertebrate Gene Control Technology [Reading Science]

Applied to Fish, Human Stem Cells, and Organoids
Web Platform Developed Using Genomes from 308 Species

A South Korean research team has successfully expanded the application scope of ‘conditional gene knockout (cKO)’ technology, which selectively turns off gene function only at specific time points, from fish to human stem cells and organoids. With the ability to precisely control even essential genes for survival at desired moments, the potential for use in disease research and regenerative medicine is expected to grow.

The Genome Editing Research Center at the Institute for Basic Science (IBS), led by Director Koo Bonkyoung, announced on May 20 that the team had succeeded in applying the ‘conditional gene knockout (Short Conditional intrON, SCON)’ technology—which enables selective gene function control at specific time points—to zebrafish, human induced pluripotent stem cells (iPSC), organoids, and various other biological species.

Conceptual diagram of conditional gene knockout based on the SCON system. It shows the principle where a normally functioning gene is selectively turned off when a specific enzyme operates. The research team has established the web platform "GenPos-SCON" based on the genomes of over 300 vertebrate species, and confirmed the applicability of the technology in various biological models including mice, zebrafish, human induced pluripotent stem cells (iPSC), and organoids. Provided by the research team

The research results were published online in the international journal Nucleic Acids Research on May 14.

Conditional gene knockout technology allows for the selective inactivation of specific genes only at desired times or in targeted tissues. However, previous methods were limited by their complexity and low efficiency, especially when applied to zebrafish or human stem cells.

The research team utilized the SCON technology, which involves inserting a short synthetic DNA fragment into a gene and activating a specific enzyme to turn off gene function only at the desired time. Compared to existing conditional knockout technologies, SCON features a simpler structure, making it more likely to be applied across a wide range of biological species.

In initial experiments with zebrafish, the team inserted SCON into the pigment-forming gene ‘tyrosinase (tyr)’ and observed that activating the specific enzyme caused the fish’s pigmentation to disappear. Additionally, when the function of the essential developmental gene ‘Sox2’ was inhibited by heat stimulus, abnormalities such as defective swim bladder formation and tail deformation appeared.

The team also confirmed that in human induced pluripotent stem cells, the function of genes important for cell growth and development was successfully eliminated after treatment with a chemical agent. Some cells were also observed to undergo apoptosis over time.

Experimental results of the SCON-based conditional gene knockout model. The research team successfully controlled the function of specific genes at desired time points selectively in zebrafish, human induced pluripotent stem cells (iPSC), and intestinal organoids from various animal species. Through this, they confirmed the broad applicability of the SCON technology across biological species. Provided by the research team

The researchers further explained that the SCON system functioned properly in intestinal organoids derived from mice, rats, chickens, bats, pigs, and monkeys, thereby demonstrating its broad applicability to a variety of animal species.

Additionally, the team developed ‘GenPos-SCON,’ a web platform based on the genomic data of 308 vertebrate species, to support the design of conditional gene knockout experiments. Researchers can instantly access experimental design information by entering the desired species and gene.

Koo Bonkyoung, Director of the IBS Genome Editing Research Center, said, “By expanding the application scope of this technology, we have established a foundation for conducting human disease and developmental biology research with greater precision.”

Lee Heetak, Research Fellow at the IBS Genome Editing Research Center and co-corresponding author, explained, “No matter how excellent a technology is, it has limited utility in research settings if accessibility is low. That’s why we built a platform that allows researchers to obtain experimental design information with just a few clicks.”

This content was produced with the assistance of AI translation services.