한빛사 논문
Jihye Park1,2, Jung Min Lim1, Inkyung Jung3,4, Seok-Jae Heo3,4, Jinman Park1,2, Yoojin Chang1,2, Hui Kwon Kim1,2, Dongmin Jung1, Ji Hea Yu5, Seonwoo Min6, Sungroh Yoon6,7,8, Sung-Rae Cho2,5, Taeyoung Park9,10, Hyongbum Henry Kim1,2,11,12,13,14,*
1Department of Pharmacology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
2Brain Korea 21 Plus Project for Medical Sciences, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
3Division of Biostatistics, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
4Department of Biostatistics and Computing, Graduate School, Yonsei University, Seoul 03722, Republic of Korea
5Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, South Korea
6Electrical and Computer Engineering, Seoul National University, Seoul 00826, Republic of Korea
7Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 00826, Republic of Korea
8Interdisciplinary Program in Artificial Intelligence, Seoul National University, Seoul 00826, Republic of Korea
9Department of Applied Statistics, Yonsei University, Seoul 03722, Republic of Korea
10Department of Statistics and Data Science, Yonsei University, Seoul 03722, Republic of Korea
11Center for Nanomedicine, Institute for Basic Science (IBS), Seoul, Republic of Korea
12Graduate Program of Nano Biomedical Engineering (NanoBME), Advanced Science Institute, Yonsei University, Seoul, Republic of Korea
13Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
14Lead contact
*Corresponding author
Abstract
DNA has not been utilized to record temporal information, although DNA has been used to record biological information and to compute mathematical problems. Here, we found that indel generation by Cas9 and guide RNA can occur at steady rates, in contrast to typical dynamic biological reactions, and the accumulated indel frequency can be a function of time. By measuring indel frequencies, we developed a method for recording and measuring absolute time periods over hours to weeks in mammalian cells. These time-recordings were conducted in several cell types, with different promoters and delivery vectors for Cas9, and in both cultured cells and cells of living mice. As applications, we recorded the duration of chemical exposure and the lengths of elapsed time since the onset of biological events (e.g., heat exposure and inflammation). We propose that our systems could serve as synthetic “DNA clocks.”
Keywords : DNA, clock, Cas9, CRISPR, time, temporal information, biological events, exponential decay, indel, elapsed time, timer
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