Circular RNA Immunomodulation via Intron Source Selection

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Solution Overview

Problem

Current methods fail to effectively stimulate innate immunity using circular RNAs, and there is a lack of understanding on how circular RNAs trigger immune recognition, particularly distinguishing between self and non-self circular RNAs.

Innovation Solution

Generating circular RNAs by splicing exogenous introns to stimulate innate immunity and using endogenous introns to prevent immune recognition of foreign RNA, involving techniques like backsplicing and splint ligation, and incorporating IRES elements for translation of immunogenic polypeptides.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If circular RNAs are generated by splicing exogenous introns to stimulate innate immunity, then immune activation is enhanced, but immune recognition of foreign RNA is triggered

Engineering Contradiction:

Improveimmune activationVSAvoidimmune recognition of foreign RNA

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by using different intron sources (exogenous vs. endogenous) at specific locations within the circular RNA structure to create distinct immunogenic properties. Exogenous introns are used when immune activation is desired, while endogenous introns are used when immune evasion is needed, allowing localized control of immune recognition in different applications.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent changes the parameter of intron origin (exogenous vs. endogenous) to control the immunogenicity of circular RNAs. This parameter change allows the same circular RNA structure to either stimulate or avoid immune recognition depending on the intron source, enabling flexible control of immune activation for different therapeutic purposes.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If circular RNAs are used to treat infections and cancers, then therapeutic efficacy is improved, but immune response variability increases

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidimmune response variability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent introduces dynamics by making the circular RNA design adaptable to different therapeutic contexts. By selecting appropriate intron sources and incorporating IRES elements, the system can dynamically adjust its immunogenicity profile to match the specific requirements of different diseases and patient responses, optimizing therapeutic efficacy while managing immune response variability.

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent applies universality by creating a platform technology that can treat multiple conditions (infections and cancers) using the same circular RNA methodology. The IRES element and intron splicing approach provide a universal mechanism that can be adapted across different therapeutic applications, allowing one system to serve multiple functions despite immune response variability.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20230383300A1Circular rnas and their use in immunomodulation

Publication Date: 2023.11.30 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV

AI summary

Compositions and methods of modulating an innate immune response with circular RNAs are disclosed. In particular, the disclosure relates to methods for modifying an RNA by circularization and the use of circular RNAs generated with exogenous introns to stimulate an innate immune response or circular RNAs generated with endogenous introns to prevent immune recognition of foreign RNA.