GEMS Nucleic Acid Constructs for Scalable Multi-Gene Editing

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Solution Overview

Problem

Existing gene modification techniques for cell therapies face scalability and commercial challenges, limiting their widespread availability for treating a broader spectrum of conditions and patients.

Innovation Solution

A gene editing multi-site (GEMS) construct is introduced into a genome, comprising flanking insertion sequences and a GEMS sequence with multiple nuclease recognition sequences, allowing precise insertion and integration of therapeutic proteins like chimeric antigen receptors (CARs) into safe harbor sites using CRISPR/Cas9 or Cpf1 systems.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional gene modification techniques are used for cell therapies, then therapeutic genes can be inserted into host cells, but scalability and commercial availability are limited

Engineering Contradiction:

Improvescalability of cell therapy productionVSAvoidcommercial availability of cell therapies

Core Design Contradiction:

ProductivityVSEase of manufacture

Solution Approach 1:

The GEMS construct serves multiple functions: it provides a universal platform for inserting multiple therapeutic genes simultaneously, enables scalable production through standardized multi-site integration, and facilitates commercial availability by streamlining the manufacturing process. The construct contains multiple nuclease recognition sequences that can accommodate different guide RNAs, making it a versatile tool for producing various cell therapies.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The GEMS construct is divided into distinct functional segments: flanking insertion sequences for genome integration, multiple nuclease recognition sequences for targeted editing, and guide RNA binding sites for specific gene insertion. This segmentation allows independent optimization of each function and enables modular design for different therapeutic applications.

Inventive Principle:

Principle #1Segmentation

2Adaptability or versatility

If multiple therapeutic genes are inserted into host cells using traditional methods, then treatment options for broader spectrum of conditions are expanded, but process complexity and time increase

Engineering Contradiction:

Improvespectrum of treatable conditionsVSAvoidcomplexity of gene insertion process

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The GEMS construct merges multiple nuclease recognition sequences and guide RNA binding sites into a single integrated platform. This allows simultaneous insertion of multiple therapeutic genes through a single construct, reducing the number of separate operations needed and simplifying the overall process while expanding treatment versatility.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The GEMS construct is pre-designed with multiple nuclease recognition sequences and guide RNA binding sites arranged in specific configurations. This preliminary arrangement of multiple editing sites within one construct eliminates the need for sequential operations, reducing process complexity while enabling treatment of multiple conditions.

Inventive Principle:

Principle #10Preliminary action

3Reliability

If precise integration of therapeutic genes is achieved, then expression control and stability are improved, but integration time and process steps increase

Engineering Contradiction:

Improvestable integration of therapeutic genesVSAvoidtime for gene integration process

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The GEMS construct enables self-service integration by containing all necessary elements (flanking sequences, nuclease recognition sites, guide RNA binding regions) within a single construct. The construct directs its own precise integration into the host genome through homologous recombination at the flanking sequences, eliminating the need for multiple separate steps and reducing integration time while maintaining stability.

Inventive Principle:

Principle #25Self-service

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 stable integration of therapeutic genes into host cells, facilitating scalable production of personalized cell therapies for various diseases, including cancer and autoimmune disorders, with controlled expression and high efficiency.

Implementation Method 1

said guide target sequence binds a guide polynucleotide following insertion of said GEMS construct at said insertion site

Methodology Applied

Scientific EffectComplementary base pairing: Chemical Bonding

Data Source

PatentUS12440578B2Nucleic acid constructs comprising gene editing multi-sites and uses thereof

Publication Date: 2025.10.14 IO BIOSCIENCES INC

AI summary

Disclosed herein is a polynucleotide construct comprising one or more primary endonuclease recognition sequences upstream and downstream of a multiple gene editing site that comprises a plurality of secondary endonuclease recognition sequences. The primary endonuclease recognition sequences facilitate insertion of the multiple gene editing site into a host cell genome. The secondary endonuclease recognition sequences facilitate insertion of one or more exogenous donor genes into the host cell.