Cyclic Di-Nucleotide STING Activation for Interferon Induction
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Solution Overview
Problem
There is a need for effective adjuvants that can be coformulated with antigens derived from intracellular pathogens and cancer cells to activate a robust cellular and humoral immune response, while minimizing toxic side effects, and to enhance the production of type I interferons for treating intracellular pathogens and reducing tumor burden.
Innovation Solution
Increasing the production of type I interferon in cells by increasing the level of 2′-5′ phosphodiester linkage comprising cyclic-di-nucleotides, such as cyclic-di-AMP or cyclic-di-GMP, through methods like enhancing cGAMP synthase activity or administering cyclic-di-nucleotides, which can include guanosine or adenosine nucleosides, to stimulate STING-mediated responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional adjuvants are used to stimulate immune response, then immune activation is achieved, but toxic side effects increase
Solution Approach 1:
The patent changes the chemical structure parameter of adjuvants by using cyclic-di-nucleotides with specific 2′-5′ phosphodiester linkages instead of conventional adjuvants. This structural parameter change enables selective activation of STING pathways while avoiding the toxic side effects associated with traditional adjuvants, thus resolving the contradiction between immune activation and toxicity reduction
2Reliability
If high doses of interferon are administered to treat cancer and viral infections, then treatment efficacy is improved, but toxic side effects increase
Solution Approach 1:
The patent introduces cyclic-di-nucleotides as intermediary molecules that selectively activate STING pathways to induce type I interferon production. This intermediary approach allows for controlled and specific interferon induction at lower doses, achieving treatment efficacy while minimizing the toxic side effects associated with high-dose interferon administration
3Reliability
If existing adjuvants are used to activate cellular immune response to intracellular pathogens, then some immune activation is achieved, but the response is insufficient
Solution Approach 1:
The patent changes the molecular recognition parameter by designing cyclic-di-nucleotides with specific 2′-5′ phosphodiester linkages that are specifically recognized by STING proteins. This parameter change enables potent and specific activation of cellular immune responses to intracellular pathogens, overcoming the insufficient response achieved by existing adjuvants
Data Source
AI summary
Methods and compositions are provided for increasing the production of a type I interferon (IFN) in a cell. Aspects of the methods include increasing the level of a 2′-5′ phosphodiester linkage comprising cyclic-di-nucleotide in a cell in a manner sufficient to increase production of the type I interferon (IFN) by the cell. Also provided are compositions and kits for practicing the embodiments of the methods.