Cyclic Peptide Antisense Compounds for Intracellular Delivery
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Solution Overview
Problem
Current therapeutic oligonucleotide compounds face challenges in effectively delivering therapeutic oligonucleotides to intracellular compartments to treat diseases associated with expanded CTG·CUG repeats, such as myotonic dystrophy type 1, due to limited intracellular access.
Innovation Solution
Development of compounds comprising a cyclic peptide and an antisense compound (AC) that binds to expanded CTG or CUG repeats, facilitated by an endosomal escape vehicle (EEV) to enhance intracellular localization and interaction with target gene transcripts.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If therapeutic oligonucleotide compounds are administered to treat diseases with expanded CTG·CUG repeats, then the therapeutic effect is improved, but the intracellular delivery efficiency deteriorates due to limited intracellular access
Solution Approach 1:
The patent employs cell-penetrating peptides (CPPs) as intermediary carriers that facilitate the intracellular delivery of therapeutic oligonucleotide compounds. The CPPs bind to the oligonucleotides and mediate their transport across the cell membrane, overcoming the natural barrier to intracellular access while maintaining the therapeutic oligonucleotide's ability to bind and modulate target RNA sequences associated with expanded CTG·CUG repeats
Solution Approach 2:
The invention creates composite therapeutic agents by chemically conjugating or forming complexes between cell-penetrating peptides and therapeutic oligonucleotides. This composite structure combines the cell-penetration capability of the peptide with the sequence-specific RNA-binding and modulating capability of the oligonucleotide, achieving both efficient intracellular delivery and therapeutic effect
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 compounds effectively modulate the activity and levels of genes with expanded CTG·CUG repeats, reducing the affinity of RNA-binding proteins for these transcripts, thereby restoring normal cellular function and alleviating disease symptoms.
Implementation Method 1
antisense compound (AC) that binds to expanded CUG or CTG repeats
Data Source
AI summary
Compounds comprising a cyclic peptide, such as a cyclic cell penetrating peptide, and an antisense compound are provided. The antisense compound binds to a gene having an expanded CTG repeat or a gene transcript having an expanded CUG repeat. The compounds can be delivered to subjects to treat diseases associated with expanded CTG CUG repeats, such as myotonic dystrophy type 1 (DM1), spinocerebellar ataxia-8 (SCA8), and Huntington disease like-2 (HDL2).