Off-Target Assessment for Gene Editing Therapy Suitability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The CRISPR/Cas9 gene editing technology for treating thalassemia faces challenges due to off-target effects, where mismatches during sgRNA binding to genomic DNA can cause unintended mutations at off-target sites, making it difficult to assess the suitability and effectiveness of cell therapy.
Innovation Solution
A bioinformatic prediction analysis method combined with an unbiased potential off-target site experiment analysis is used to detect and monitor off-target sites before and after administering genetically modified cells, allowing for timely assessment of gene editing events and therapy suitability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CRISPR/Cas9 gene editing technology is used to treat thalassemia, then the expression of fetal hemoglobin is increased and the disease is treated, but off-target effects occur causing unintended mutations
Solution Approach 1:
The patent applies preliminary action by performing bioinformatic prediction analysis and unbiased potential off-target site experiment analysis before administering the cell therapy. This pre-screening identifies potential off-target sites, allowing the researchers to assess and mitigate risks before the actual gene editing treatment is applied to patients.
Solution Approach 2:
The patent implements feedback by monitoring off-target sites after the cell therapy is administered. Through tracking and monitoring the potential off-target sites identified earlier, the system provides feedback on whether gene editing events occur at these sites, enabling continuous assessment of treatment safety and effectiveness.
2Measurement precision
If off-target sites are monitored after cell therapy administration, then the suitability of therapy can be assessed, but the complexity of the evaluation process increases
Solution Approach 1:
The patent applies segmentation by dividing the off-target assessment into distinct phases: bioinformatic prediction analysis to identify potential sites, unbiased experiment analysis to validate sites, and post-therapy monitoring of specific tagged sites. This segmentation makes the complex evaluation process more manageable and systematic.
Solution Approach 2:
The patent uses preliminary action by constructing an off-target tagged site model before therapy administration. This pre-established model identifies and tags specific sites that need monitoring, simplifying the post-therapy assessment process by focusing only on pre-identified potential off-target sites rather than analyzing the entire genome.
Data Source
AI summary
Disclosed is a method for determining the suitability of a cell therapy for an individual. By means of using a bioinformatic method and an experimental analysis method for an unbiased potential off-target site, a potential off-target site of a genetically modified cell from an individual is predicted before administering a cell therapy to an individual, and the potential off-target site is monitored after administering, to the individual, the genetically modified cell from the individual to determine whether gene editing occurs at the potential off-target site and to evaluate the suitability of the therapy on the basis of the occurrence of a gene editing event.