Cyclic Cell-Penetrating Peptide Conjugates for Intracellular Delivery
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Solution Overview
Problem
Current antisense compounds face challenges in accessing intracellular compartments and achieving targeted tissue distribution, leading to limited effectiveness in treating diseases associated with aberrant gene transcription, splicing, and trinucleotide repeats due to off-target interactions and inefficient delivery.
Innovation Solution
Development of compounds comprising a therapeutic moiety and a cell-penetrating peptide (CPP), such as cyclic CPP, conjugated with an endosomal escape vehicle (EEV), which targets polyadenylation sequence elements to modulate gene expression by enhancing intracellular delivery and avoiding off-target effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If antisense compounds are administered systemically, then they can reach target tissues, but they have limited ability to access intracellular compartments and achieve wide tissue distribution
Solution Approach 1:
The patent uses composite materials by combining antisense compounds with cell-penetrating peptides (CPPs) and endosomal escape vehicles (EEVs) to create a multi-component delivery system. This composite approach enables the compound to both reach target tissues systemically and efficiently access intracellular compartments, resolving the contradiction between tissue distribution and intracellular delivery efficiency
Solution Approach 2:
The patent introduces cell-penetrating peptides and endosomal escape vehicles as intermediary components that facilitate intracellular delivery. These intermediaries bridge the gap between systemic administration and intracellular target access, improving delivery efficiency without compromising tissue distribution
2Reliability
If antisense compounds are designed for high specificity, then off-target interactions are minimized, but delivery efficiency to intracellular compartments remains limited
Solution Approach 1:
The patent merges the antisense compound (providing specificity) with cell-penetrating peptides and endosomal escape vehicles (providing delivery efficiency). This combination allows the system to maintain high specificity while achieving efficient intracellular delivery, resolving the contradiction between specificity and productivity
3Ease of operation
If current delivery systems are used, then administration is simplified, but effectiveness in treating diseases with aberrant gene transcription is limited
Solution Approach 1:
The patent incorporates endosomal escape vehicles that perform preliminary action by pre-equipping the compound with the ability to escape endosomes before reaching the target. This preliminary preparation ensures effective intracellular delivery and therapeutic effectiveness while maintaining simplified administration through systemic delivery
Data Source
AI summary
Compounds that include a cyclic cell penetrating peptide and a therapeutic moiety that modulates polyadenylation of a gene transcript. The therapeutic moiety may be an antisense compound (AC) that binds a target gene transcript. The AC may bind to at least a portion of a polyadenylation signal element (PSE) or may bind in sufficiently close proximity to the PSE to modulate polyadenylation of the target gene transcript. Methods include administering the aforementioned compounds to cells or subjects to modulate diseases or conditions.