STING Agonists for Sustainable Immune Response
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Solution Overview
Problem
Current treatments for viral and bacterial infections, including cancer, often fail to adequately activate the immune system, leading to incomplete or unsustainable responses, and existing therapies for chronic hepatitis B virus infection are ineffective in clearing the virus and inducing long-term immunity.
Innovation Solution
Development of novel STING agonists and modulators that activate the STING pathway to enhance innate and adaptive immune responses, potentially used in combination with other therapeutics to improve treatment efficacy and specificity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments are used for viral and bacterial infections, then the treatment can be administered with existing therapies, but the immune system activation is insufficient leading to incomplete or unsustainable responses
Solution Approach 1:
The patent modifies the chemical structure of cyclic dinucleotides by introducing various substitutions and analogues to enhance their ability to activate STING. This structural parameter change increases the potency and sustainability of immune response activation compared to natural CDNs
Solution Approach 2:
The invention combines cyclic dinucleotide structures with different chemical groups and modifications to create composite molecular entities that simultaneously enhance STING activation while improving pharmacological properties for sustained immune response
2Reliability
If existing therapies are used for chronic hepatitis B virus infection, then the treatment can be applied with current standard care, but the virus cannot be cleared and long-term immunity is not induced
Solution Approach 1:
The patent employs cyclic dinucleotides to preemptively activate the STING pathway and establish robust immune memory before viral challenges occur. This preliminary immune activation creates sustained protection that clears persistent viral infections like chronic hepatitis B
Solution Approach 2:
The invention uses modified cyclic dinucleotides as intermediary molecules that bridge the gap between pathogen detection and sustained immune activation. These CDN intermediaries activate STING to produce type I interferons and establish long-term immunity against hepatitis B virus
3Quantity of substance
If STING agonists are used to activate the immune system, then robust and sustainable immune responses are induced, but the treatment mechanism becomes more complex compared to existing therapies
Solution Approach 1:
The patent develops cyclic dinucleotide analogues that universally activate STING across different cell types and infection contexts. This multi-functional approach allows a single therapeutic mechanism to address various viral and bacterial infections while maintaining manageable complexity
Solution Approach 2:
The invention segments the immune activation process into distinct phases: initial STING activation by CDN, type I interferon production, and sustained immune response. This segmentation allows for better understanding and control of the treatment mechanism's complexity
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
The use of STING agonists can induce robust and sustainable immune responses, effectively treating cancers, viral diseases, and bacterial infections by activating the STING pathway, potentially offering improved outcomes compared to existing therapies.
Implementation Method 1
The mechanism by which cGAMP activates the immune response is through its binding to the endoplasmic reticulum bound protein STING and its activation. STING activation triggers a downstream signaling cascade that results in activation of cytosolic kinases IKK and TBK1, which activates the transcription factors NF-kB and IRF3, respectively.
Data Source
AI summary
A class of phosphorus containing polycyclic compounds of general formula I, of general formula I′ or of general formula I″, wherein B1, B2, R1, R2, R1′, X1, X2, Y1, Y2, BL1, BL2, Z1, and Z2 are defined herein, that may be useful as modulators of type I interferon production, specifically as STING modulating agents, are provided. Also, provided are use of such compounds.