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New Genome Editing Breakthrough Enables Partial Inhibition of Gene Function

Kumamoto University researchers successfully demonstrated the practical application of the CRISPR-Cas9 technique for fine-tuning gene activity

Researchers at Kumamoto University have successfully executed a practical trial of groundbreaking genome-editing technique (Fig. 1) that allows for the partial inhibition of essential gene function without causing lethality. This innovative approach, which leverages CRISPR-Cas9 technology, opens new doors for genetic research and agricultural advancements by enabling the study and modification of genes that were previously difficult to analyze.

A New Way to Study Essential Genes

Genes that are crucial for survival often pose a challenge for researchers, as completely disabling them can be fatal to the organism. Traditional gene knockout methods, including CRISPR-Cas9, typically result in complete loss of function, making it difficult to investigate these vital genetic components. To address this limitation, the research team led by Associate Professor Takashi Ishida, Faculty of Advanced Science and Technology, Kumamoto University, conceived a method to introduce hypomorphic mutations, which reduce—but do not entirely eliminate—gene function.
Using the model plant Arabidopsis thaliana, the team successfully applied their method to the HPY2 gene, which is essential for cell division and plant growth. While complete loss of this gene results in seedling lethality, the newly engineered hypomorphic mutants exhibited delayed growth but remained viable (Fig. 2), paving the way for researchers to analyze gene function in greater detail in future studies.

Applications for Agriculture and Beyond

This breakthrough has significant implications beyond basic genetic research. By fine-tuning gene activity instead of completely disabling genes, this technique could be used to enhance desirable traits in crops without causing harmful side effects. For example, modifying genes responsible for stress resistance in plants could lead to crops that are more resilient to climate change while maintaining their growth and yield.
“This method provides a powerful tool for studying genes that were previously inaccessible due to their essential nature,” said Associate Professor Ishida. “It also opens up new possibilities for precision breeding in agriculture, where controlled gene modification is key to improving traits without unintended consequences.

Fig. 1 CRISPR-Cas9-mediated mutation at mRNA splicing site


Fig. 2 Phenotypes of wile type, hpy2 hypomorphic mutant and hpy2 null mutant

Reference
Authors Mika Yoshimura, Takashi Ishida*
Title of original paper
 
Generation of viable hypomorphic and null mutant plants via CRISPRCas9 targeting mRNA splicing sites
Journal Journal of Plant Research
DOI 10.1007/s10265-024-01597-2

 

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