Muscle-Specific Peptide Conjugates for Targeted Drug Delivery
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Solution Overview
Problem
Current therapeutic compounds face challenges in selectively targeting specific organs or tissues, leading to undesirable side effects due to non-specific uptake in the body, particularly in muscle diseases like Duchenne muscular dystrophy and spinal muscular atrophy, where poor delivery of antisense oligonucleotides and recombinant enzymes results in inadequate treatment efficacy.
Innovation Solution
Development of peptides and peptidomimetics that selectively bind to and are taken up by muscle cells, including the heart, allowing for improved in vivo uptake of therapeutic compounds such as antisense oligonucleotides and recombinant enzymes by conjugating them with muscle-specific peptides, enhancing delivery efficiency and reducing toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If therapeutic compounds are delivered through circulation to target organs or tissues, then the treatment can reach the target site, but the compounds will also be taken up by other organs and tissues causing undesirable side effects
Solution Approach 1:
The patent applies the intermediary principle by introducing targeting molecules (such as antibodies, peptides, or ligands) that specifically bind to receptors on the surface of target cells. These targeting molecules act as mediators between the therapeutic compound and the target tissue, directing the compound to the desired location while preventing non-specific distribution throughout the body. This resolves the contradiction by improving targeting specificity without increasing systemic toxicity.
Solution Approach 2:
The patent implements local quality by modifying the therapeutic compound to have different properties in different locations. Through conjugation with targeting molecules, the compound gains location-specific binding capabilities, allowing it to maintain high affinity for target tissues while having reduced interaction with non-target organs. This creates a spatial gradient of effectiveness that improves reliability while minimizing harmful effects.
2Productivity
If antisense oligonucleotides are delivered systemically to treat muscle diseases, then broad muscle coverage can be achieved, but the uptake into muscle tissues is poor resulting in inadequate treatment efficacy
Solution Approach 1:
The patent applies composite materials by creating conjugates that combine antisense oligonucleotides with muscle-specific targeting molecules. This composite structure integrates the gene-silencing capability of the oligonucleotide with the muscle-tissue affinity of the targeting molecule, achieving both high delivery efficiency to muscle tissues and effective treatment of muscle diseases. The composite nature allows simultaneous optimization of both productivity and reliability.
Solution Approach 2:
The patent implements parameter changes by modifying the chemical and physical properties of the oligonucleotide through conjugation. The targeting molecule alters the biodistribution, cellular uptake, and tissue penetration parameters of the oligonucleotide, transforming it from a poorly absorbed molecule into one that efficiently reaches muscle tissues. This parameter optimization resolves the contradiction between delivery efficiency and treatment efficacy.
3Reliability
If compounds are coupled to targeting molecules to improve uptake into targeted tissue, then the effectiveness increases, but the complexity of the compound increases
Solution Approach 1:
The patent applies segmentation by dividing the therapeutic system into distinct functional modules: the therapeutic compound (antisense oligonucleotide or drug), the targeting molecule (antibody, peptide, or ligand), and the conjugation linker. This modular segmentation allows each component to be optimized independently for its specific function while maintaining overall system effectiveness. The complexity is managed through functional separation rather than creating a single complex molecule.
Solution Approach 2:
The patent uses an intermediary conjugation linker to connect the therapeutic compound and targeting molecule. This intermediary component simplifies the overall structure by providing a standardized interface for attachment, avoiding the need to create highly complex direct fusion proteins. The linker acts as a buffer that maintains the functional integrity of both components while enabling their association, thus improving effectiveness without proportionally increasing complexity.
Data Source
AI summary
The invention provides conjugates, comprising an organ, tissue or tumor cell homing molecule linked to a moiety. Such a moiety can be, for example, an oligonucleotide, small interfering RNA, gene, virus, protein, pharmaceutical or detectable agent. In addition the invention provides methods to diagnose or treat a pathology of the muscle or heart, by administrating to a subject having or suspected of having a pathology a molecule or conjugate that homes to, binds to and is taken up by the muscle cells or heart cells.