CRISPR/Cas9 Synthetic DNA Clock for Long-Term Time Measurement
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Solution Overview
Problem
Current methods for measuring time in living organisms, particularly in biology, lack accuracy for long periods such as weeks, and existing DNA-based methods have limitations in resolution and recordable time range.
Innovation Solution
A method and system using the CRISPR/Cas9 system to measure time by transducing a composition for editing target genes in cells, culturing them, and sequencing target sequences to calculate elapsed time based on indel frequency, with the equation F=1−IF=e−λ(t−t0), where F is the relative frequency of an intact target sequence, IF is the indel frequency, λ is the indel generation rate, and t0 is the latent time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If electrical or mechanical methods are used to measure time in modern life sciences, then measurement can be performed with existing technology, but accurate measurement of long periods (weeks) cannot be achieved
Solution Approach 1:
The patent replaces electrical and mechanical time measurement methods with a biological system based on DNA mutation accumulation. The CRISPR-Cas9 system creates indels at a known rate, and sequencing these mutations provides a biological clock that accurately measures time over weeks to months, overcoming the limitations of conventional electrical/mechanical methods for long-term measurement.
Solution Approach 2:
The patent changes the measurement parameter from electrical signals to molecular biological parameters (DNA sequence variations). By monitoring the accumulation of indels in target genes over time and using the exponential decay model F=1-IF=e^(-λ(t-t0)), the system transforms time measurement into a molecular clock mechanism that operates accurately over extended periods.
2Loss of information
If DNA-engineering tools are used to record temporal information in DNA, then time information can be stored in genetic material, but resolution and recordable time range remain limited
Solution Approach 1:
The patent segments the time measurement function into multiple independent target genes, each accumulating indels independently. By monitoring multiple genes simultaneously and combining their mutation data, the system achieves higher temporal resolution and extends the recordable time range beyond what single-gene methods can provide.
Solution Approach 2:
The patent implements a feedback mechanism where the measured indel frequency is continuously compared against the exponential decay model to calculate elapsed time. This feedback loop allows for accurate time reconstruction and verification, improving both resolution and the reliability of stored temporal information.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables accurate measurement of time elapsed from a defined point, allowing for the recording of time information ranging from hours to weeks in animal cells and living animals, and provides a synthetic biological clock for recording exposure time to chemicals and lifespan.
Implementation Method 1
transducing a composition for editing target genes into cells... sequencing target sequences from the genomic DNA of the cells... measuring an indel frequency (IF) of the target sequence
Data Source
AI summary
The present invention relates to a method for recording the passage of time in DNA of cells. More specifically, the present invention relates to a method for measuring time which has elapsed from a predetermined time point in cells using target genome editing system, and to a system for measuring time in cells. The method of the present invention is a new synthetic biological clock that enables the accurate in vivo measurement of the time which has elapsed from a defined time point to any time point. Through the system of the present invention, time information ranging from hours to weeks can be accurately recorded in vitro or in vivo in DNA of animal cells and living animals, and the time which has elapsed from a recorded time point can be measured at an unknown time point through DNA sequencing. Also, when the synthetic DNA clock of the present invention is used, it is possible to accurately record and measure the exposure time of cultured cells to chemicals and the lifespan of living animals remaining after time starts to be recorded in the living animals. In addition, temporal information regarding various intracellular signal transductions can be recorded and decoded in DNA in the cells using the synthetic DNA clock of the present invention.