CRISPR/Cas DNA Molecular Event Logging

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Solution Overview

Problem

Current methods lack the ability to efficiently record and store molecular events and their timing within cells, limiting the capability to log internal and external stimuli in a stable and heritable manner.

Innovation Solution

The use of CRISPR/Cas systems and TALENs for precise gene editing enables the incorporation of specific polynucleotide sequences into cellular DNA, creating a record of molecular events through homology-directed repair (HDR), allowing for the integration of timing indicators to provide a temporal log of cellular experiences.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If CRISPR/Cas systems and TALENs are used for precise gene editing to record molecular events, then the ability to log internal and external stimuli is improved, but the device complexity increases

Engineering Contradiction:
Improverecording precisionVSAvoidsystem complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent introduces an intermediary recording system where CRISPR/Cas systems and TALENs act as mediators between molecular events and the DNA record. These gene editing tools enable precise incorporation of polynucleotide sequences that encode information about sensed states or stimuli, resolving the contradiction by providing a sophisticated intermediary mechanism that achieves high recording precision while managing system complexity through modular biological components

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs copying by creating DNA-based records that replicate information about molecular events. Through homology-directed repair (HDR), the system copies sensed states into stable polynucleotide sequences that can be heritably passed to subsequent cellular generations, achieving precise measurement through informational copying rather than direct physical measurement

Inventive Principle:
Principle #26Copying

2Stability of the object's composition

If polynucleotide sequences are incorporated into cellular DNA to create stable records, then the stability and heritability of recorded information is improved, but the manufacturing precision requirements increase

Engineering Contradiction:
Improverecord stabilityVSAvoidintegration precision
Core Design Contradiction:
Stability of the object's compositionVSManufacturing precision

Solution Approach 1:

The patent applies preliminary action by pre-designing polynucleotide sequences with specific properties before incorporation into cellular DNA. The recording system is configured in advance to respond to particular molecular events, and the polynucleotide sequences are prepared with appropriate homology regions to ensure precise integration through HDR, thereby achieving both stability and manufacturing precision

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent utilizes parameter changes by modifying DNA sequences at specific locations through controlled gene editing. The system changes the molecular state of the DNA by incorporating distinct polynucleotide sequences that encode different information about sensed events, achieving stable records through controlled parameter changes in the genetic material

Inventive Principle:
Principle #35Parameter changes

3Loss of information

If timing indicators are integrated into the recording system, then the temporal information capability is improved, but the device complexity increases

Engineering Contradiction:
Improvetemporal informationVSAvoidlogging system complexity
Core Design Contradiction:
Loss of informationVSDevice complexity

Solution Approach 1:

The patent merges multiple recording functions into a unified DNA-based logging system. By combining event detection, timing indication, and information storage into a single polynucleotide record, the system reduces overall complexity while preserving temporal information. The merged system uses integrated polynucleotide sequences that simultaneously encode both the molecular event and its timing

Inventive Principle:
Principle #5Merging (Combining)

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

This approach allows for the stable recording and heritability of molecular events and their timing within cells, enabling the creation of a temporal log that can be read through DNA sequencing, enhancing our understanding of cellular states and responses.

Implementation Method 1

A new polynucleotide sequence may be inserted into the DSB using homology directed repair ("HDR").

Methodology Applied
Scientific EffectHomology-directed repair (HDR):

Data Source

PatentEP3636758B1Timing of logged molecular events
Publication Date: 2021.06.16 MICROSOFT TECHNOLOGY LICENSING LLC
  • EP3636758B1 patent drawingFigure 1
  • EP3636758B1 patent drawingFigure 2
  • EP3636758B1 patent drawingFigure 3

AI summary

A log of molecular events experienced by a cell and timing indicators for those events are stored in existing polynucleotides through a process of creating a double strand break ("DSB") in a polynucleotide and inserting a new polynucleotide sequence by repairing the DSB with homology directed repair ("HDR"). The presence, order, and number of new polynucleotide sequences provides a log of events and timing of those events. Cellular mechanisms for creating the DSB and/or repairing with HDR are regulated by intra- or extracellular signals. When the log is created in the DNA of a cell, the changes may be heritably passed to subsequent generations of the cell. A correlation between the cellular signals and sequence of inserted HDR templates allows for identification of events and the timing experienced by the cell.