Adenovirus Protein VI Peptide-Polymer Complex for Intracellular Delivery
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current oncolytic adenoviruses used in cancer treatment face limitations in systemic administration due to rapid immune removal, low targeting efficiency to tumor tissues, and hepatotoxicity, leading to reduced therapeutic effects, especially in metastatic cancer cases.
Innovation Solution
A peptide comprising the amino acid sequence mVI and RKKRRQRRR is used for intracellular delivery of viral DNA or viruses, enhancing their efficiency and specificity to tumor cells, combined with biocompatible polymers like PEG and polyamidoamine to form complexes that facilitate systemic administration and improve therapeutic outcomes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If oncolytic adenoviruses are administered systemically, then the therapeutic effect can spread throughout the body, but the viruses are rapidly removed by immune cells in the blood
Solution Approach 1:
The patent uses peptide-polymer complexes as intermediary carriers to transport adenovirus DNA into tumor cells. The peptide component (derived from adenovirus protein VI) and polymer (such as polyamidoamine or PEG) form a complex that mediates the delivery process, protecting the viral DNA from immune recognition while enabling systemic administration. This intermediary mechanism resolves the contradiction by allowing systemic delivery without direct viral circulation.
Solution Approach 2:
Instead of administering the viral virus itself, the patent uses a copy of the viral genetic material (adenovirus DNA) delivered through peptide-polymer complexes. This copying approach allows the therapeutic effect to be achieved without the risks associated with circulating live viruses, thereby enabling systemic administration while avoiding immune-mediated removal.
2Adaptability or versatility
If oncolytic adenoviruses are administered systemically, then cancer treatment can reach metastatic sites, but very little therapeutic reaches the target tumor tissue
Solution Approach 1:
The peptide-polymer complex exhibits local quality through its ability to specifically interact with tumor cell surfaces. The peptide component binds to receptors on tumor cells, and the polymer component facilitates endocytosis and intracellular delivery. This localized interaction mechanism ensures that while the complex can be administered systemically, the actual therapeutic delivery is concentrated at the target tumor tissue, resolving the contradiction between systemic accessibility and target-specific delivery.
Solution Approach 2:
The peptide-polymer complex acts as an intermediary that bridges the gap between systemic circulation and target tumor tissue. The complex first circulates in the bloodstream (systemic administration) then specifically interacts with tumor cells through peptide-receptor binding and polymer-mediated internalization, ensuring efficient delivery to the target while maintaining systemic accessibility.
3Adaptability or versatility
If oncolytic adenoviruses are administered systemically, then cancer can be treated throughout the body, but hepatotoxicity occurs due to accumulation in the liver
Solution Approach 1:
By using adenovirus DNA instead of live virus particles, the patent eliminates the replication and accumulation issues that cause hepatotoxicity. The DNA form does not replicate in the liver or other non-target tissues, thereby preventing the harmful accumulation that leads to hepatotoxicity while still enabling systemic administration for treating cancer throughout the body.
Solution Approach 2:
The peptide-polymer complex serves as an intermediary delivery system that protects the viral DNA from non-specific interactions with liver cells. The complex facilitates targeted delivery to tumor cells through peptide-receptor binding and endocytosis, preventing the DNA from accumulating in the liver or other non-target tissues, thereby eliminating hepatotoxicity while maintaining systemic administration capability.
4Productivity
If adenovirus DNA is delivered to tumor cells, then intracellular delivery efficiency improves, but the delivery method must be safer and more efficient than conventional virus administration
Solution Approach 1:
The peptide-polymer complex is designed as an intermediary delivery system that achieves high intracellular delivery efficiency while maintaining safety. The peptide component (adenovirus protein VI-derived) and polymer (polyamidoamine or PEG) work together to facilitate efficient endocytosis and intracellular release of viral DNA, while the complex structure prevents non-specific interactions and toxic effects, thereby meeting both efficiency and safety requirements.
Solution Approach 2:
The patent modifies the delivery parameters by changing the physical and chemical properties of the delivery system. The peptide-polymer complex alters size, charge, and surface properties compared to conventional virus administration. These parameter changes enable efficient cellular uptake and intracellular delivery while improving safety by reducing immune recognition and non-specific tissue interactions.
Data Source
Figure 1~2
Figure 3~4
Figure 5~6
AI summary
The present invention relates to a composition for intracellular delivery containing an adenovirus protein VI-derived peptide and an anticancer pharmaceutical composition containing the same. According to the present invention, the use of the peptide or peptide-polymer composite of the present invention improves intracellular delivery efficiency of a nucleic acid, a peptide, a polypeptide, an antibody, a chemical material, or a virus. Therefore, the peptide or peptide-polymer composite of the present invention can be favorably used as an intracellular delivery system for various therapeutics.