Species-Selective CRISPR Microbiota Editing for Immune Modulation
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Solution Overview
Problem
Existing immune cell therapies, such as CAR-T cell approaches, face challenges with dose titration and potential adverse events like cytokine release syndrome due to the lack of control over immune cell activity, and there is a need for targeted modulation of immune responses in diseases mediated by immune cells.
Innovation Solution
The use of guided nucleases, such as CRISPR/Cas systems, to selectively target and alter specific microbiota species in the patient, causing microbiota dysbiosis to modulate immune cell therapies and treat conditions like autoimmune diseases, inflammatory diseases, and viral infections.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If broad-spectrum antibiotics are used to alter microbiota, then immune cell therapy can be modulated, but related beneficial microbiota species are also eliminated
Solution Approach 1:
The patent applies local quality by designing CRISPR/Cas systems with species-specific guide RNAs that target only particular microbiota species. This allows selective modification of target species while leaving other microbiota species unaffected, thereby achieving immune cell therapy modulation without eliminating beneficial microbiota. The specificity is achieved through tailored CRISPR guides that recognize unique genomic sequences in target species.
Solution Approach 2:
The patent uses CRISPR/Cas systems as an intermediary tool between the desire to modulate immune cell therapy and the need to preserve beneficial microbiota. Rather than directly applying broad-spectrum antibiotics, the CRISPR system acts as a precise mediator that enables selective targeting of specific microbiota species, thus achieving the therapeutic goal while avoiding collateral damage to beneficial microbes.
2Reliability
If immune cell activity is enhanced to improve therapeutic efficacy, then treatment effectiveness increases, but adverse events like cytokine release syndrome increase
Solution Approach 1:
The patent implements feedback control by using microbiota-derived signals to naturally regulate immune cell activity. By modulating specific microbiota species, the system creates a feedback loop where microbiota composition influences immune cell behavior, allowing the immune response to be enhanced or suppressed based on the physiological state, thereby improving therapeutic efficacy while reducing the risk of excessive immune activation and adverse events.
Solution Approach 2:
The patent applies dynamics by enabling flexible modulation of immune cell activity through controlled alterations in microbiota composition. Rather than static enhancement of immune cells, the system allows dynamic adjustment of immune responses based on microbiota state, enabling the therapeutic effect to adapt to changing conditions and reducing the likelihood of uncontrolled immune activation leading to adverse events.
3Reliability
If adoptive cell therapy is used to treat advanced cancer, then remarkable responses are generated, but the approach is restricted to small clinical trials
Solution Approach 1:
The patent applies universality by combining adoptive cell therapy with CRISPR-mediated microbiota modulation, creating a multi-functional approach that can be applied across different cancer types and patient populations. The microbiota modulation component serves multiple functions: enhancing immune cell efficacy, reducing adverse events, and providing a standardized protocol that can be implemented in larger clinical trials beyond specialized centers.
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 allows for precise modulation of immune cell activities by altering the microbiota, reducing adverse events and enhancing therapeutic efficacy in conditions like autoimmune diseases and viral infections, while sparing related species and strains.
Implementation Method 1
selective targeting of a first microbiota species or strain, or archaeal species or strain, in a microbiota using guided nuclease (e.g. CRISPR/Cas) cutting of a respective target sequence in host cells
Data Source
AI summary
The invention relates to methods of modulating immune cells in a patient by altering microbiota of the patient. The invention also relates to methods of modulating treatments or therapies in a subject organism by altering microbiota of the subject. The invention also relates to cell populations, systems, arrays, cells, RNA, kits and other means for effecting this. In an example, advantageously selective targeting of a particular species in a human gut microbiota using guided nucleic acid modification is carried out to effect the alteration.