CRISPR/Cas9 Endogenous Gene Editing for Cell Therapy
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Solution Overview
Problem
Current cell therapy technologies face limitations in precisely controlling cell function, particularly in gene therapy, where adding extra genetic material to human genomes is challenging, and there is a need for precise regulation of gene expression to address various diseases effectively.
Innovation Solution
The use of the CRISPR/Cas9 system to engineer modified cells by replacing or deleting endogenous genes, allowing for precise modification of DNA at specific sites and creating cells that can respond to environmental cues by producing therapeutic molecules in response to pathological signals, such as inflammatory cytokines, thereby providing a self-regulated therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional gene therapy approaches are used to add functional copies of genes to patient cells, then genetic diseases may be treated, but the ability to precisely control cell function is limited
Solution Approach 1:
The patent changes the fundamental parameter of gene modification from adding extra genetic material to precisely editing endogenous genes. CRISPR/Cas9 enables targeted modifications at specific genomic locations, allowing precise control of gene expression levels, timing, and spatial distribution. This parameter change transforms gene therapy from a粗放 approach to a precision medicine approach, directly addressing the limitation in controlling cell function.
Solution Approach 2:
The patent replaces traditional mechanical gene delivery methods (viral vectors, physical transfection) with a programmable molecular system. CRISPR/Cas9 uses guide RNA sequences to direct the Cas9 nuclease to specific DNA targets, substituting mechanical random insertion with programmable site-specific editing. This substitution enables precise control over where and how genes are modified, improving reliability while reducing uncontrolled variability.
2Manufacturing precision
If extra genetic material is added to human genomes through gene therapy, then functional gene copies are provided, but precise regulation of gene expression is difficult to achieve
Solution Approach 1:
The patent introduces CRISPR/Cas9 as an intermediary system between the researcher's intent and the genomic modification outcome. The guide RNA acts as an intermediary that translates the target sequence information into precise nuclease recruitment, enabling controlled editing. Additionally, the system allows intermediates such as homology-directed repair templates to mediate precise gene insertion or modification, providing fine-tuned control over the final genetic outcome and expression regulation.
3Adaptability or versatility
If synthetic transcription factors are engineered to target any DNA sequence, then gene activation and repression can be controlled, but traditional gene therapy challenges remain
Solution Approach 1:
The patent creates a universal gene editing platform where CRISPR/Cas9 can target any DNA sequence by simply changing the guide RNA sequence. This multi-functional system can activate, repress, or modify any gene of interest, providing universal applicability across different diseases and cell types. The same core machinery (Cas9 nuclease) serves multiple functions through programmable guidance, enhancing versatility while maintaining reliable, mechanism-based editing through the well-characterized CRISPR pathway.
Data Source
AI summary
Disclosed herein are compositions and methods for cell therapy comprising an engineered cell. The present invention is directed to a composition for treating a subject having or suspected of having a disease, the composition comprising a modified cell comprising a modified endogenous gene, wherein an endogenous gene or fragment thereof is replaced with a transgene using a CRISPR/Cas9 system to generate the modified endogenous gene, the modified cell having an altered response to a cell signal or stimulus.