HEV-Like Particle Capsids for Targeted Cargo Delivery
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Solution Overview
Problem
Existing virus-like particle (VLP) systems face challenges such as passive cell uptake, premature degradation, toxicity, and insufficient association with theranostic molecules, limiting their effectiveness in diagnostic and therapeutic applications.
Innovation Solution
Development of HEV-VLPs with modified surface protruding domains for conjugating functional peptides or compounds, capable of encapsulating small molecule drug products, DNA and RNA molecules, and inorganic beads, and designed for targeted drug delivery and immunomodulation, using baculovirus expression vectors in insect cells to produce functional VLPs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional VLP systems are used for targeted delivery, then delivery capability is achieved, but cell uptake is passive and degradation occurs prematurely
Solution Approach 1:
The patent applies parameter changes by modifying amino acid sequences in the capsid proteins of VLPs to enhance their stability and resistance to degradation. Specific substitutions, insertions, or deletions in the protein sequence alter the structural and functional parameters of VLPs, improving their reliability for targeted delivery while reducing premature degradation in biological environments.
2Reliability
If conventional VLP systems are used, then therapeutic delivery is achieved, but toxicity issues arise
Solution Approach 1:
The patent applies local quality by introducing specific amino acid modifications at targeted locations within the capsid protein structure. These localized changes improve therapeutic effectiveness through enhanced stability and reduced immunogenicity, while minimizing toxicity by avoiding widespread structural alterations that could compromise safety.
3Reliability
If conventional VLP systems are used, then cargo delivery is achieved, but association with theranostic molecules is insufficient
Solution Approach 1:
The patent applies universality by designing VLPs with modified capsid proteins that possess multiple functional capabilities. The amino acid modifications enable the VLPs to associate more effectively with various theranostic molecules while maintaining their core delivery function, thereby enhancing both reliability and adaptability for diverse therapeutic and diagnostic applications.
Data Source
AI summary
Virus-Like Particles derived from the subfamilies, Parahepevirinae, which infect trout and salmon, and the Orthohepevirinae, which infect mammals and birds, particularly those of the species Paslahepevirus balayani, which can cause acute hepatitis in humans and several mammalian species, and chronic conditions in immunocompromised patients are also disclosed. Major aspects of the invention relate to compositions of Virus-Like Particles comprising viral capsid proteins capable of assembly in cultured cells that may be purified, disassembled, and reassembled in the presence of other molecules suitable for use as therapeutic drug products to facilitate the targeting and delivery of cargo molecules to specific cells or tissues, or as antigenic agents designed to stimulate responses to heterologous epitopes exposed on the surfaces of Virus-Like Particles. Preferred aspects relate to functional capsids comprising polypeptide sequences comprising one or more amino acid substitutions, insertions, or deletions of amino acid encoded by a consensus of ORF2 genes, wherein said variant polypeptides are functionally-similar or have enhanced properties compared to capsid polypeptides encoded by naturally-occurring viruses obtained from clinical samples or prototype Hepatitis E Viruses (HEV). Other aspects include the design and assembly of modified vectors to facilitate the basic and applied studies leading to the development and commercialization of novel drug products, and as tools advancing the interests of institutions involved in animal and human healthcare.