Beta Globin Locus Deletion to Raise Fetal Hemoglobin
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Solution Overview
Problem
Current treatments for hemoglobinopathies, such as β-thalassemias and sickle cell anemia, are limited and there is a need for safe and effective therapies to increase fetal hemoglobin production.
Innovation Solution
Genome editing using DNA endonucleases and guide RNAs to introduce single- or double-strand breaks in the human beta globin locus, resulting in a permanent deletion and increased production of fetal hemoglobin.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If genome editing is used to delete beta globin locus and increase fetal hemoglobin production, then effectiveness of treatment is improved, but device complexity and difficulty of implementation increase
Solution Approach 1:
The patent uses guide RNAs as intermediaries to direct DNA endonucleases to specific locations in the beta globin locus. The guide RNAs serve as mediators between the editing machinery and the target genome sequence, enabling precise deletion of the beta globin locus while increasing fetal hemoglobin production without requiring complex manual genome manipulation
Solution Approach 2:
The patent replaces traditional mechanical or chemical methods of inducing genome deletions with a biological system using DNA endonucleases and guide RNAs. This substitution allows for site-specific editing of the beta globin locus with high precision, achieving effective treatment while the complexity is managed through the specificity of the molecular recognition system
2Reliability
If multiple treatments are required to achieve therapeutic effect, then treatment effectiveness may be improved, but loss of time and treatment duration increase
Solution Approach 1:
The patent designs the genome editing system to create permanent deletions of the beta globin locus in hematopoietic stem cells, which then permanently produce increased levels of fetal hemoglobin. This preliminary genetic modification eliminates the need for repeated treatments, as the therapeutic effect is established once and maintained throughout the patient's life
Solution Approach 2:
The patent targets the deletion of the beta globin locus, effectively discarding the defective gene that causes hemoglobinopathies. By removing the problematic genetic element permanently, the system recovers therapeutic benefit through increased fetal hemoglobin production without requiring ongoing treatment interventions
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 leads to a significant increase in fetal hemoglobin levels, potentially ameliorating the symptoms of hemoglobinopathies with a single treatment.
Implementation Method 1
introducing into the human cell one or more deoxyribonucleic acid (DNA) endonucleases to effect one or more single-strand breaks (SSBs) or double-strand breaks (DSBs), within or near the human beta globin locus on chromosome 11
Implementation Method 2
introducing into the human cell one or more deoxyribonucleic acid (DNA) endonucleases and one or more single-molecule guide RNA (sgRNAs) to effect one or more single-strand breaks (SSBs) or double-strand breaks (DSBs)
Data Source
AI summary
Materials and methods for treating a patient with hemoglobinopathy, both ex vivo and in vivo and materials and methods for deleting at least a portion of a human beta globin locus on chromosome 11 in a human cell by genome editing and thereby increasing the production of fetal hemoglobin (HbF).