LNP-Replicon RNA Oncolytic Composition for IL-12 Tumor Immunity

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Existing cancer treatments lack effective methods to trigger a robust anti-cancer immune response at local tumors and induce systemic immunity against distal tumors.

Innovation Solution

A synthetic oncolytic virus comprising a lipid nanoparticle and a self-amplifying replicon RNA encoding an IL-12 molecule is injected at a tumor site, which induces immunogenic cell death and systemic immunity by encapsulating the replicon RNA within lipid nanoparticles to deliver IL-12, leveraging the synergistic effects of lipid nanoparticles and replicon RNA to enhance immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional cancer treatments are used, then tumor growth is controlled to some extent, but they fail to trigger robust anti-cancer immune response at local tumors and induce systemic immunity against distal tumors

Engineering Contradiction:

Improveanti-cancer immune responseVSAvoidtumor growth inhibition

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent combines lipid nanoparticles with self-amplifying replicon RNA encoding IL-12 to create a synthetic oncolytic virus. This merging of delivery vehicle (LNP) and therapeutic agent (replicon RNA) enables both targeted delivery to local tumors and systemic immune activation, resolving the contradiction between reliable immune response and effective tumor growth inhibition.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The invention uses a composite structure consisting of lipid nanoparticles encapsulating replicon RNA. This composite material allows the system to simultaneously achieve targeted delivery (through LNP properties) and sustained immune stimulation (through self-amplifying replicon RNA), thereby triggering both local and systemic anti-cancer immunity effectively.

Inventive Principle:

Principle #40Composite materials

2Reliability

If lipid nanoparticles are used to deliver IL-12, then immunogenic cell death is triggered and immune response is enhanced, but the complexity of the treatment system increases

Engineering Contradiction:

Improveimmune response activationVSAvoidtreatment system complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The self-amplifying replicon RNA encodes its own replication machinery and can autonomously replicate within tumor cells after delivery by lipid nanoparticles. This self-service capability eliminates the need for continuous external administration or complex delivery systems, reducing treatment system complexity while maintaining reliable immune response activation.

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The lipid nanoparticle serves multiple functions: it protects the replicon RNA from degradation, facilitates cellular uptake, and can be formulated with standard lipid components. This multi-functionality reduces the need for additional complex delivery mechanisms, simplifying the overall treatment system while ensuring reliable immune activation.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Duration of action of stationary object

If self-amplifying replicon RNA is used, then sustained IL-12 expression is achieved and systemic immunity is induced, but the manufacturing precision requirements increase

Engineering Contradiction:

ImproveIL-12 expression durationVSAvoidreplicon RNA sequence precision

Core Design Contradiction:

Duration of action of stationary objectVSManufacturing precision

Solution Approach 1:

The patent modifies specific parameters of the replicon RNA sequence (such as promoter strength, coding sequence optimizations, and stability elements) to enhance IL-12 expression duration and efficiency. By carefully tuning these parameters during design, the system achieves sustained expression without requiring excessive manufacturing precision, as the self-amplifying nature provides robustness against minor variations.

Inventive Principle:

Principle #35Parameter changes

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 synthetic oncolytic virus effectively triggers an anti-cancer immune response at local tumors and elicits systemic immunity against distal tumors, inhibiting tumor growth and preventing recurrence.

Implementation Method 1

The lipid nanoparticle is capable of triggering immunogenic cell death

Methodology Applied

Scientific EffectImmunogenic cell death:

Implementation Method 2

a self-amplifying replicon RNA comprising a sequence that encodes an interleukin (IL)-12 molecule. The IL-12 molecule is expressed by the self-amplifying replicon RNA

Methodology Applied

Scientific EffectGene expression:

Data Source

PatentUS20260061013A1Synthetic oncolytic LNP-replicon RNA and uses for cancer immunotherapy

Publication Date: 2026.03.05 MASSACHUSETTS INST OF TECH

AI summary

The present disclosure relates to synthetic oncolytic viruses comprising a lipid nanoparticle comprising one or more types of lipid and a self-amplifying replicon RNA comprising a sequence that encodes an immunomodulatory molecule.