The Korea Research Institute of Bioscience & Biotechnology (KRIBB) said its researchers have developed a technology that can maximize the existing CRISPR-Cas12a gene scissors' properties to recognize targets selectively.

Researchers have found a more accurate CRISPR gene scissor method. They are, from left, Professors Lee Seung-hwan and Kim Sun-wook at KRIBB, and Professor Lee Dong-seok at Kyungpook National University. (KRIBB)

The CRISPR-Cas12a system, also known as gene scissors, is a type of immune system found in bacteria and archaea and is known to bind to target DNA to induce double helix cleavage. The technology is commonly used for genome editing in living organisms.

Researchers commonly use CRISPR-Cas12a gene scissors complementarily with the CRISPR-Cas9 gene scissors by recognizing a different nucleotide sequence from CRISPR-Cas9, problems of unintentionally cutting a specific gene. Non-target cutting has become an issue to supplement when applying the technology to the human body as gene therapy.

To improve the CRISPR-Cas12a gene scissors' target specificity, the team, led by Professors Lee Seung-hwan and Kim Sun-wook at the state research institute, developed a method to dramatically reduce non-target cleavage by substituting DNA for a specific nucleotide sequence in the CRISPR-Cas12a construct. Professor Lee Dong-seok at Kyungpook National University also participated in the study.

The researchers conducted tests to confirm that the target specificity in various gene targets significantly increased when using the CRISPR-Cas12a gene scissors when a specific nucleotide sequence end of the CRISPR-Cas12a construct was replaced with DNA.

"This study reveals that the target specificity of the genetic scissors can be innovatively increased by replacing the end of a specific sequence of the CRISPR genetic scissors construct with DNA," Professor Lee said. "The method developed in the research can be applied to a variety of gene scissor systems that operate based on guide RNA, and will make a significant contribution in terms of safety improvement in the development of gene therapy products."

The journal Nucleic Acids Research has published the results of the study.

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