CRISPR/Cas Guide RNA Combinations for T Cell Editing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Gene-editing efficacy in CRISPR-based systems for T cells is highly unpredictable, especially when editing multiple genes, limiting the effectiveness of adoptive cell therapies for cancers.
Innovation Solution
The use of CRISPR/Cas systems comprising SOCS1-targeting and PTPN2-targeting gRNA molecules, which together demonstrate enhanced gene-editing efficiency comparable to or exceeding individual gRNA systems, for modifying immune effector cells to treat various cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If CRISPR-based systems are used to edit multiple genes in T cells, then the effector functions of T cells can be enhanced, but the gene-editing efficacy becomes highly unpredictable
Solution Approach 1:
The patent segments the gene-editing process by targeting and editing specific genes (SOCS1 and PTPN2) separately and systematically. Each gene is edited with specific gRNA sequences designed to achieve predictable outcomes, transforming the unpredictable multi-gene editing into controlled segmentary modifications that can be individually optimized and combined reliably
Solution Approach 2:
The patent applies parameter changes by optimizing specific editing parameters including gRNA sequences, Cas9 mutations, and editing conditions to achieve predictable and reliable gene editing. By carefully controlling these parameters, the system transforms the unpredictability of multi-gene editing into a reliable process with consistent efficacy
2Productivity
If multiple genes are targeted for editing simultaneously, then therapeutic effectiveness can be improved, but the unpredictability of editing efficacy increases
Solution Approach 1:
The patent performs preliminary actions by pre-designing and pre-optimizing gRNA sequences for each target gene before combining them into a multi-gene editing system. This preliminary optimization of individual editing components ensures that when multiple genes are edited simultaneously, the overall efficacy remains predictable and reliable
Solution Approach 2:
The patent uses an intermediary approach by employing a vector system that delivers multiple gRNA-Cas9 complexes to cells in a controlled manner. This intermediary delivery mechanism ensures that each gene is edited with consistent precision, maintaining manufacturing precision even when multiple genes are targeted simultaneously
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 CRISPR/Cas system with combined SOCS1 and PTPN2 targeting gRNAs achieves at least 50% to 90% of the gene-editing efficiency of single-target systems, enhancing immune cell functions and improving cancer treatment outcomes.
Implementation Method 1
guide RNA molecules, which together demonstrate enhanced guide RNA molecules, which together demonstrate enhanced gene-editing efficiency
Data Source
AI summary
The present disclosure provides gRNA compositions, CRISPR/Cas systems comprising the same, and methods of their use in the modification of immune effector cells. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.