Polyalkyleneimine RNA Polyplexes for Stable Intramuscular Delivery

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Solution Overview

Problem

Existing methods for delivering RNA, particularly self-replicating RNA, face challenges related to safety concerns, unsatisfactory gene expression levels, and regulatory and technological hurdles, limiting their clinical application.

Innovation Solution

A composition comprising single-stranded RNA and polyalkyleneimine, formulated as polyplex particles, which can be frozen, lyophilized, or spray-dried, ensuring stability and compliance with pharmaceutical standards, and enabling efficient intramuscular delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If RNA is delivered using non-viral delivery vehicles, then safety concerns are reduced, but gene expression levels are unsatisfactory

Engineering Contradiction:

Improvesafety concernsVSAvoidgene expression levels

Core Design Contradiction:

Object-affected harmful factorsVSProductivity

Solution Approach 1:

The patent changes the chemical parameters of the delivery vehicle by using polyalkyleneimine with specific molecular weights (1-100 kDa) and controlling the N:P ratio (2:1 to 10:1), which optimizes both safety and gene expression levels simultaneously

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite polyplex formulation combining polyalkyleneimine with RNA, where the polymer-RNA complex structure enables both safe delivery and efficient gene expression through synergistic effects of the components

Inventive Principle:

Principle #40Composite materials

2Productivity

If RNA is administered intramuscularly, then delivery efficiency is improved, but formulation stability is compromised

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidformulation stability

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The patent adjusts formulation parameters including ionic strength (50 mM or less), pH (4-8), and polyalkyleneimine molecular weight to maintain stability during intramuscular administration while preserving delivery efficiency

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent incorporates stabilizing agents and optimizes formulation conditions beforehand to protect against degradation during storage and administration, ensuring RNA remains stable while maintaining intramuscular delivery efficiency

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

3Duration of action of stationary object

If polyplex particles are frozen or lyophilized, then shelf life is extended, but RNA activity may be lost

Engineering Contradiction:

Improveshelf lifeVSAvoidRNA activity

Core Design Contradiction:

Duration of action of stationary objectVSReliability

Solution Approach 1:

The patent modifies formulation parameters such as ionic strength, pH, and the presence of stabilizing agents to enable freezing and lyophilization while preserving RNA activity and functionality

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent incorporates cryoprotectants and stabilizing agents in the formulation beforehand to protect RNA from degradation during freezing and lyophilization processes, ensuring activity is maintained after storage

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

4Productivity

If viral delivery vehicles are used, then delivery efficiency is high, but safety concerns arise

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidsafety concerns

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent uses polyalkyleneimine as an intermediary non-viral delivery vehicle that mediates RNA delivery to cells through electrostatic interactions, achieving viral-like efficiency without viral safety concerns

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs a non-viral polyalkyleneimine carrier that can be easily produced, is biodegradable, and does not require the complex safety monitoring of viral vectors, providing a safer alternative with maintained delivery efficiency

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

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 formulation provides safe and efficient delivery of RNA, maintaining activity and stability, suitable for immunotherapeutic applications, including vaccination against infectious diseases and cancer.

Implementation Method 1

The polyplex particles comprise single stranded RNA, preferably self-replicating or self-amplifying RNA, and a polyalkyleneimine

Methodology Applied

Scientific EffectElectrostatic interaction: Electrostatics

Data Source

PatentUS20250213599A1Formulation for administration of RNA

Publication Date: 2025.07.03 BIONTECH SE

AI summary

The present invention relates to compositions comprising polyplex formulations for delivery of RNA to a target organ or a target cell after parenteral administration, in particular after intramuscular administration. More precisely, the present invention relates to formulations for administration of RNA such as self-replicating RNA, in particular by intramuscular injection. In more detail, the formulations comprise polyplex particles from single stranded RNA and a polyalkyleneimine.