Multiplex Cell Genome Editing with Orthogonal Tools and Lipid Nanoparticles

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Solution Overview

Problem

Existing methods for multiplex genome editing in cells face challenges such as poor cell survival, increased translocations, and decreased efficiency due to cumulative toxicity, limiting the quality and yield of genetically modified cell products.

Innovation Solution

The use of at least two orthogonal genome editing tools, such as a base editor and an RNA-guided cleavase, delivered via lipid nanoparticles, allows for simultaneous multiplex genome editing with improved cell survival and expansion, reducing the time and steps required for manufacturing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If multiple genome editing tools are delivered simultaneously to a cell, then multiplex genome editing efficiency is improved, but cell survival decreases due to cumulative toxicity

Engineering Contradiction:

Improvemultiplex genome editing efficiencyVSAvoidcell survival

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent segments the delivery of multiple genome editing tools by delivering them in separate steps rather than simultaneously. The first genome editing tool is delivered and allowed to act, then the second genome editing tool is delivered subsequently. This temporal segmentation reduces cumulative toxicity to the cell while still achieving multiplex editing, thereby improving cell survival while maintaining editing efficiency.

Inventive Principle:

Principle #1Segmentation

2Reliability

If sequential editing process is used to perform multiple edits, then cell toxicity is reduced, but manufacturing time increases and yield decreases

Engineering Contradiction:

Improvecell qualityVSAvoidmanufacturing yield

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent merges the delivery of multiple genome editing tools into a single step using a single LNP formulation that contains both tools, while maintaining sequential action through temporal separation of their delivery. This combining approach reduces manufacturing steps and time while achieving high editing efficiency and cell yield, resolving the contradiction between quality and productivity.

Inventive Principle:

Principle #5Merging (Combining)

3Adaptability or versatility

If multiple genome edits are performed in different loci, then gene editing versatility is improved, but translocation frequency increases

Engineering Contradiction:

Improvegene editing versatilityVSAvoidtranslocation frequency

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent segments the execution of multiple genome edits temporally by delivering editing tools in separate steps. The first edit is performed, then the second edit is performed subsequently. This temporal segmentation allows multiple loci to be edited while reducing the simultaneous stress on the cell that causes translocations, thereby maintaining versatility while reducing harmful effects.

Inventive Principle:

Principle #1Segmentation

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 enhances editing efficiency and cell viability, resulting in higher yields of genetically modified cells suitable for therapeutic applications.

Implementation Method 1

delivered via lipid nanoparticles

Methodology Applied

Scientific EffectLipid nanoparticle delivery:

Data Source

PatentUS20250276090A1Methods and Compositions for Genetically Modifying a Cell

Publication Date: 2025.09.04 INTELLIA THERAPEUTICS INC

AI summary

Methods and compositions for genetically modifying a cell are provided.