Trimeric Peptide-Oligonucleotide Conjugates for Antisense Delivery
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Solution Overview
Problem
Current antisense technology oligonucleotides and peptide-oligonucleotide-conjugates have limitations in terms of antisense or antigene performance, necessitating the development of improved compounds for therapeutic, diagnostic, and research applications.
Innovation Solution
The development of trimeric peptide-oligonucleotide-conjugates, where an oligonucleotide is covalently bound to a trimeric peptide, enhancing the delivery and efficacy of oligonucleotides into cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If oligonucleotides are used for antisense therapy, then gene expression can be modulated, but cellular uptake and delivery efficiency are limited
Solution Approach 1:
The invention creates a composite material by covalently conjugating oligonucleotides with trimeric cell-penetrating peptides. This composite structure combines the gene-modulating capability of oligonucleotides with the cell-penetration ability of peptides, achieving both reliable antisense performance and improved cellular uptake efficiency
Solution Approach 2:
The trimeric cell-penetrating peptide acts as an intermediary that facilitates the delivery of oligonucleotides into cells. The peptide conjugate serves as a mediator that enables efficient cellular uptake while maintaining the oligonucleotide's antisense function
2Productivity
If single CPP-oligonucleotide conjugates are used, then delivery is improved, but efficacy is still limited compared to trimeric conjugates
Solution Approach 1:
The invention merges three cell-penetrating peptide units with the oligonucleotide to form a trimeric conjugate. This combination enhances both delivery efficiency and therapeutic efficacy by providing multiple cell-penetration domains that work synergistically to improve cellular internalization and functional performance
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 trimeric peptide-oligonucleotide-conjugates demonstrate improved cellular uptake and efficacy compared to unconjugated oligonucleotides and single CPP-oligonucleotide conjugates, potentially leading to more effective therapeutic outcomes.
Implementation Method 1
an antisense compound, e.g., an oligonucleotide, which hybridizes to a target nucleic acid, modulates gene expression activities
Implementation Method 2
trimeric peptide-oligonucleotide-conjugates comprising an oligonucleotide covalently bound to a trimeric peptide
Data Source
AI summary
Provided herein are oligonucleotides, trimeric peptides, and peptide-oligonucleotide-conjugates. Also provided herein are methods of treating a muscle disease in a subject in need thereof, comprising administrating to the subject oligonucleotides, trimeric peptides, and peptide-oligonucleotide-conjugates described herein.