Cell Penetrating Peptide Carrying Dual Oligonucleotide Cargo
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Antisense and RNAi oligonucleotides face poor delivery and uptake into cells, limiting their therapeutic efficacy due to associated cellular toxicity from delivery agents.
Innovation Solution
Attaching specific combinations of two oligonucleotide cargo molecules to a cell-penetrating peptide (CPP) without eliminating delivery capability, allowing for reduced toxicity and enhanced biological activity by targeting multiple sequences simultaneously.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a delivery agent is used to improve cellular delivery of oligonucleotides, then delivery efficiency is improved, but cellular toxicity increases
Solution Approach 1:
The invention extracts and removes the delivery agent from the system by using naked oligonucleotides without any delivery agents, conjugates or complexes. The oligonucleotides are administered alone to achieve both improved safety profile and acceptable delivery efficiency, eliminating the toxicity problem while maintaining therapeutic function
Solution Approach 2:
The invention segments the therapeutic system into separate components: the oligonucleotide therapeutic agent is delivered independently without being conjugated to delivery agents. This segmentation allows the oligonucleotide to function therapeutically while avoiding the toxic effects associated with delivery agents
2Reliability
If a single oligonucleotide is attached to CPP, then delivery is achieved, but therapeutic efficacy is limited due to poor uptake
Solution Approach 1:
The invention merges multiple oligonucleotide cargo molecules (two or more) onto a single cell-penetrating peptide carrier. This combining approach enables simultaneous delivery of multiple therapeutic agents into cells, thereby enhancing overall therapeutic efficacy while maintaining delivery capability through the CPP
Solution Approach 2:
The cell-penetrating peptide is designed as a universal multi-functional carrier that can simultaneously transport multiple different oligonucleotide cargo molecules. This multi-functionality allows a single CPP to deliver diverse therapeutic agents (antisense oligonucleotides, RNAi oligonucleotides, etc.) to achieve broader therapeutic effects
3Productivity
If higher concentration of CPP is used to improve delivery, then uptake increases, but toxicity increases
Solution Approach 1:
By combining multiple oligonucleotide cargo molecules onto a single CPP, the invention increases the therapeutic payload delivered per CPP molecule. This allows achieving effective therapeutic levels with lower CPP concentrations, thereby reducing toxicity while maintaining or enhancing cellular uptake and therapeutic efficacy
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 approach enables effective delivery and biological activity of oligonucleotides at lower CPP concentrations, reducing toxicity and expanding treatment capabilities for multiple patient sub-groups with similar RNA-related diseases.
Implementation Method 1
a cell penetrating peptide arranged in the N to C terminal direction
Implementation Method 2
each said oligonucleotide comprises a sequence which specifically hybridises to a target sequence
Data Source
AI summary
The present invention relates to cell penetrating molecules comprising two oligonucleotide cargo molecules.