Nucleic acid system to specifically reprogram b and t cells and uses thereof
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Solution Overview
Problem
Current treatments for autoimmune diseases and certain cancers are inadequate as they do not address the underlying causes, leading to inefficiencies and side effects, and there is a need for treatments that can stimulate or suppress immune responses based on specific disease signals, while being adaptable to various diseases involving the immune system.
Innovation Solution
A nucleic acid system is developed to reprogram B or T cells using a lentiviral vector, encoding a sensor that recognizes pathological ligands, a transducer that activates upon binding, and a transducer/effector component that produces therapeutic effector molecules, allowing for signal-specific regulation and localized production of proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for autoimmune diseases and cancers, then treatment can be administered, but they do not address underlying causes leading to inefficiencies and side effects
Solution Approach 1:
The treatment is segmented into distinct functional modules: sensor components that detect specific pathological signals, transducer components that convert signals into cellular responses, and effector components that execute therapeutic functions. This modular architecture allows selective targeting of disease-causing pathways while sparing healthy processes, thereby improving effectiveness and reducing side effects.
Solution Approach 2:
The reprogrammed immune cells exhibit local quality by being activated only in response to specific pathological signals detected by their sensor components. This signal-specific activation ensures that therapeutic effects are localized to diseased tissues or pathological conditions, avoiding systemic side effects while maintaining treatment reliability.
2Measurement precision
If immune cells are genetically reprogrammed to enhance recognition capacity, then they can more precisely distinguish pathological environments, but the system complexity increases
Solution Approach 1:
The genetic circuit is divided into separate functional modules: sensor modules for detecting specific pathological signals, transducer modules for signal conversion, and effector modules for therapeutic output. This segmentation allows each module to be optimized independently for its specific function, improving recognition precision while managing overall system complexity through modular design.
Solution Approach 2:
The synthetic circuit architecture serves multiple functions: it can detect various pathological signals through different sensor configurations, transduce diverse input signals through common signaling pathways, and execute multiple therapeutic effector functions. This multi-functionality allows a single reprogrammed cell type to address different diseases or conditions, reducing the need for multiple specialized cell types.
3Duration of action of stationary object
If lentiviral vectors are used to transduce synthetic circuits into immune cells, then long-term therapy is achieved, but the manufacturing process becomes more complex
Solution Approach 1:
Multiple genetic elements required for long-term expression and circuit function are merged into a single lentiviral vector construct. This includes the synthetic circuit components, selectable markers, and regulatory elements all integrated into one transducible unit, simplifying the manufacturing process while ensuring stable long-term expression in reprogrammed immune cells.
Solution Approach 2:
The lentiviral vector is pre-engineered with all necessary genetic elements for stable integration and long-term expression before transduction. This preliminary preparation of the vector system ensures that once immune cells are transduced, the synthetic circuit remains stably expressed and functional for extended periods, achieving long-term therapy without requiring complex post-transduction modifications.
Data Source
AI summary
The invention relates to a nucleic acid system comprising a sensor component and a transducer/effector component that allows to specifically reprogram B and T cells. The inventors successfully demonstrated that upon binding of target molecules on the dedicated sensor (targeting a given pathological signal), the transducer pNR4A1 was specifically activated leading to the expression of the effector therapeutic molecules placed under its control. The main advantage of this system is its full programmability in terms of recognized signal and output functions, which can be adapted to the targeted diseases. As such, the invention may be applied to many pathologies, such as tumors, auto immune disorders, transplantation rejection, allergies, neurological disorders, and infectious diseases.