Controlling DNA recombination reactions in mice using external light irradiation

  The University of Tokyo in Japan announced that they have successfully developed a new technology that can efficiently control the DNA recombination reaction by irradiating weak light for a short time.

  A team of distinguished researcher Kono Fuyun from the Graduate School of Comprehensive Culture, University of Tokyo, graduate student Okazaki Risako, Associate Professor Sato Moratoshi, Columbia University’s Rehabilitation and Regenerative Medicine and Pharmacology Professor Yazawa Masato completed the relevant research.

  When knocking out the base sequence of the target gene from the genome, or when inserting genes into the genome, most researchers will use the Cre-LoxP recombinase system technology. In recent years, the technology of using compounds and light to control the Cre-LoxP recombinase system has attracted more and more people’s attention. Especially if light can be used to control the Cre-LoxP recombinase system, it can be achieved with specific biological Target tissues and cells to induce DNA recombination at any point in time. However, when the existing technology uses light to control, it will greatly reduce the efficiency of DNA recombination, which is also a major problem that has consistently plagued researchers.

  In this research, the team members connected the temporarily inactive DNA recombinase (Cre) with a light switch protein, and successfully developed a light-activated Cre recombinase that can use light to control the DNA recombination reaction. The enzyme is named "PA-Cre".

  PA-Cre can be produced by irradiating weak light (one hundred thousandth of the light intensity commonly used in optogenetics), achieving DNA recombination with extremely high efficiency, and a short time of about 30 seconds is sufficient to induce DNA recombination. In addition, the researchers successfully used PA-Cre to recombine DNA at the selected target location.

  On this basis, the researchers used PA-Cre to optically control the genetic genes in the deep body of mice. Experiments have found that when light is irradiated from outside the organism using a non-invasive method, the liver deep in the mouse body can also induce DNA recombination with high efficiency.

  Researchers said that this result allows gene activities in living organisms to be controlled by non-invasive light irradiation, which is of great significance to the discovery of disease-related gene functions.