RIAA RNA Construct for RIG-I Activation Without Interferon
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Solution Overview
Problem
Current treatments using cytotoxic cells for cancer and viral infections face limitations due to insufficient load of granzyme B and perforin, and existing RIG-I agonists induce unwanted interferon responses.
Innovation Solution
Development of a specific RNA construct, RIAA, which binds to RIG-I to increase perforin and granzyme B levels in cytotoxic cells without inducing interferon response, administered ex vivo or in vivo for enhanced therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing RIG-I agonists are used to increase perforin and granzyme B load, then the therapeutic efficacy of cytotoxic cells is improved, but unwanted interferon response and inflammatory response occur
Solution Approach 1:
The patent segments the function of RIG-I agonists by designing a specific RNA construct (56 RNA subunits with hairpin and loop structures) that selectively activates RIG-I for perforin and granzyme B production without triggering the interferon response pathway. This segmentation allows independent optimization of cytotoxic cell activation while avoiding unwanted inflammatory effects.
Solution Approach 2:
The RNA construct is designed with specific local structural qualities (hairpin and loop structures with particular base compositions) that enable selective binding to RIG-I. This local quality differentiation allows the construct to activate RIG-I's cytotoxic granule release function while avoiding activation of interferon-producing pathways.
2Ease of operation
If cytokine exposure is used to activate cytotoxic cells in vitro prior to adoptive transfer, then cell activation is achieved, but sufficient serial killing capacity is not obtained due to limited perforin and granzyme B load
Solution Approach 1:
The patent applies preliminary action by administering the RIG-I agonist RNA construct to cytotoxic cells before adoptive transfer to increase their perforin and granzyme B load in advance. This preliminary enhancement of cytotoxic granule content ensures that cells have sufficient killing capacity upon transfer, overcoming the limitation of standard cytokine activation protocols.
3Ease of manufacture
If standard adoptive cell transfer protocols are used, then treatment is administered, but insufficient perforin and granzyme B load limits the therapeutic effectiveness
Solution Approach 1:
The patent changes the parameter of cytotoxic granule load by introducing the RIG-I agonist RNA construct that specifically increases perforin and granzyme B content in cytotoxic cells. This parameter change transforms standard adoptive cell transfer into an enhanced protocol with sufficient therapeutic efficacy while maintaining ease of administration.
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
RIAA significantly enhances the viability, killing power, and efficacy of cytotoxic cells, overcoming obstacles in adoptive cell transfer and providing effective treatment for various cancers and viral infections.
Implementation Method 1
A central step for the load of cytolytic granules is the activation of the intracellular RNA recognition sites such as MDA-5 (melanoma differentiation factor 5) and Rig-I (retinoic acid-inducible gene I)
Data Source
AI summary
The present invention comprises Rig I agonists for enhancing the effects of cytotoxic cells and stem Cells. The Rig I agonists can be used in vivo as small molecule therapeutics or in vitro to enhance cells for adoptive cell transfer. Applications include cancer therapy, immune system enhancement, chronic viral infection and treatment of viral induced inflammation and enhancement of virus based therapies.