Awakening in vivo dormant rejuvenation-inducing genes through CRISPR/dCas9 activator
Challenging the realization of a sophisticated and safe dream of immortality... Published in Aging Cell (IF11.5), a world-renowned academic journal

Calico and Altos Labs, recently formed by Google and Amazon, are working on projects to fulfill the dream of immortality, with the overarching goal of extending life by turning the biological clock backward. Cell rejuvenation and regeneration technology, which induces rejuvenation by setting the biological clock of adult cells backward, is gaining tremendous attention globally. 

Professor Kim Jong-pil's team at Dongguk University has developed a technology that induces more sophisticated and safe cell rejuvenation and regeneration by delicately activating the endogenous dormant rejuvenation-inducing gene (Oct4) using cutting-edge gene editing/scissors technology for the first time in the world. The Oct4 gene is a dormant gene that is no longer expressed in adult cells, despite its importance in the early development of human embryos. Professor Kim Jong-pil's team confirmed that temporarily reactivating only the Oct4 gene to reset an elderly mouse's biological clock using gene editing/scissors technology-based gene expression induction technology in an aged mouse converted the aging-inducing proteins and epigenome to a younger state, rejuvenating them to the same condition as a young mouse. 

Because there are adverse effects that generate tumor growth and cancer induction, existing cell reprogramming technology has clear limits in creating therapeutic and human cell regeneration/rejuvenation treatment technology. To overcome the limitations of current technology, Professor Kim Jong-pil's team produced cell rejuvenation in old mice by triggering the expression of a single gene (Oct4) with sophisticated genetic scissors while avoiding the production of tumor-producing genes (c-Myc and Klf4). As a result, it was possible to minimize tumorigenic side effects while reliably and efficiently inducing rejuvenation in old cells and tissues, hence extending lifetime. 

For the first time in the world, Professor Kim Jong-pil, who was in charge of this research, could efficiently express in vivo dormant rejuvenation-inducing genes in cells and tissues using genetic scissors technology. This resulted in rejuvenation and regeneration in all tissues of the aging mouse. Notably, this method has been demonstrated to have the potential to be used for a variety of degenerative disorders. Above all, it presented a significant opportunity to use human disease treatment technologies via anti-aging rejuvenation. 

This study was published on March 25, 2023, in Aging Cell (IF: 11.5), a world-renowned academic publication, with funding from the pan-governmental regenerative medical technology project group and the university’s important research institution project.

- Journal Title: Transcriptional activation of endogenous Oct4 via the CRISPR/dCas9 activator ameliorates Hutchinson-Gilford Progeria Syndrome in mice
- Author Information: Kim Jong-pil (correspondent, Dongguk University professor), Kim Jun-yeop (first author, doctoral student), Hwang Ye-rim (first author, doctoral student)

* For inquiries regarding this material, please contact the Dongguk University Department of Chemistry Professor Kim Jong-pil (02-2260-3321, jk2316@gmail.com).