DNA Typewriter Prime Editor Multiplex Recording

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Solution Overview

Problem

Existing DNA recording technologies, such as CRISPR-Cas-based base editors, are limited in their ability to write various base sequence patterns, making multiplex recording difficult.

Innovation Solution

A novel DNA Typewriter system using a CRISPR-Cas-based prime editor and a DNA tape with disrupted and active monomers, allowing for long-term time recording and multiplex recording.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If CRISPR-Cas-based base editors are used for DNA recording, then the recording function is achieved, but the ability to write various base sequence patterns is limited

Engineering Contradiction:

Improveability to write various base sequence patternsVSAvoidrecording function

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The invention changes the editing mechanism from base substitution (base editors) to insertion/deletion (prime editors), enabling diverse base sequence patterns to be written while maintaining recording functionality through disrupted PAM sequences

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The DNA tape is segmented into repeating monomer units, each capable of independent recording events, allowing multiplex recording of various biological signals simultaneously

Inventive Principle:

Principle #1Segmentation

2Loss of information

If DNA recording technologies are used, then biological information can be stored, but monomer deletions occur reducing recording accuracy

Engineering Contradiction:

Improverecording accuracyVSAvoidmonomer deletion stability

Core Design Contradiction:

Loss of informationVSReliability

Solution Approach 1:

The invention designs the DNA tape with disrupted PAM sequences that prevent guide RNA binding after editing, cushioning against unwanted subsequent edits and monomer deletions that would compromise recording accuracy

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

3Adaptability or versatility

If CRISPR-Cas-based systems are used for recording, then time measurement is enabled, but multiplex recording capability is difficult to achieve

Engineering Contradiction:

Improvemultiplex recording capabilityVSAvoidsystem complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The prime editor system serves multiple functions: it edits the DNA tape, disrupts PAM sequences to prevent re-binding, and enables multiplex recording of different biological signals, reducing the need for separate systems for each function

Inventive Principle:

Principle #6Universality (Multi-functionality)

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

The system effectively measures and estimates elapsed time in cells by inserting specific sequences into the DNA tape, minimizing monomer deletions and maintaining recording accuracy over time.

Implementation Method 1

a prime editor protein or a nucleic acid encoding the same

Methodology Applied

Scientific EffectReverse transcription:

Data Source

PatentUS20250027173A1DNA clocks capable of long-term timekeeping comprising a composition for measuring or predicting the duration of cellular events in cells

Publication Date: 2025.01.23 IND ACADEMIC COOP FOUND YONSEI UNIV

AI summary

Disclosed are a DNA clock capable of recording long periods of time, comprising a composition for measuring or estimating elapsed time in cells, and a method of measuring or estimating elapsed time in cells using the composition.