Polymeric Modification Agent for Break-Free Genetic Editing
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Solution Overview
Problem
Current gene editing and genome engineering methods face limitations in versatility and precision, often requiring DNA breaks that can lead to off-target effects and chromosomal rearrangements, and are not effective for multi-nucleotide changes or deletions.
Innovation Solution
The use of a polymeric modification agent, such as a DLR molecule, that binds to DNA without causing breaks, combined with a sequence modification polynucleotide, to achieve genetic modifications by temporarily stalling replication and utilizing mismatch repair and replication fork restart mechanisms for targeted nucleotide changes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If DNA breaks are introduced for gene editing, then genetic modification can be achieved, but off-target effects and chromosomal rearrangements occur
Solution Approach 1:
The invention extracts and removes the harmful DNA breakage step from the gene editing process. The system achieves genetic modification through template-directed repair of stalled replication forks without requiring double-strand breaks, thereby eliminating off-target effects and chromosomal rearrangements while maintaining precise genetic modification capability
Solution Approach 2:
The invention introduces an intermediary mechanism (stalled replication fork with template DNA) to mediate genetic modification. Instead of directly breaking DNA, the system uses a stalled replication fork as an intermediary structure that allows template-directed repair, achieving precise genetic modification without the harmful effects of direct DNA breakage
2Adaptability or versatility
If conventional gene editing methods are used, then some genetic modifications can be achieved, but versatility for multi-nucleotide changes and deletions is limited
Solution Approach 1:
The invention creates a universal gene editing system that can perform multiple functions including multi-nucleotide changes, deletions, and insertions. The stalled replication fork mechanism serves as a universal platform that accommodates various types of genetic modifications through template-directed repair, greatly enhancing versatility while maintaining precision
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 enables precise and efficient genetic modifications with minimal off-target effects, allowing for versatile gene editing and engineering without introducing DNA breaks, thereby enhancing the safety and efficacy of gene therapy applications.
Implementation Method 1
a polymeric modification agent, such as a DLR molecule, that binds to DNA without causing breaks
Implementation Method 2
achieve genetic modifications by temporarily stalling replication and utilizing mismatch repair and replication fork restart mechanisms
Implementation Method 3
utilizing mismatch repair and replication fork restart mechanisms for targeted nucleotide changes
Data Source
AI summary
The present disclosure provides technologies for genetic modification without a need for introduction of one or more breaks into any genetic material being modified.