Fibril Peptide RTIFIISM Enhances Viral Uptake
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Solution Overview
Problem
Current methods for introducing nucleic acids into target cells, such as those using viruses or cationic polymers, face limitations in efficiency and stability, particularly with peptides like SEVI, which are expensive and prone to aggregation, necessitating improved peptide-based solutions for enhanced gene transfer.
Innovation Solution
A fibril peptide consisting of 8 to 20 amino acids, specifically the sequence RTIFIISM or sequences at least 75% identical thereto, forms fibrils that enhance virus infection by associating with viral particles, improving uptake into host cells with low immunogenicity and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If SEVI peptide is used to enhance viral infection, then infection efficiency is improved, but production cost increases and aggregation occurs
Solution Approach 1:
The invention segments the SEVI peptide sequence into a shorter core motif (amino acids 248-286 of prostatic acid phosphatase) that retains fibril-forming and infection-enhancing properties. This segmentation reduces the peptide length from 39 residues to a more manageable size, lowering production costs while maintaining the ability to form nanofibrils that enhance viral infection.
Solution Approach 2:
The patent develops a simplified peptide sequence that can be produced more cheaply than the full-length SEVI peptide. The shorter sequence requires fewer resources for synthesis and purification, making it a cost-effective alternative that achieves similar biological function without the burden of producing and storing large amounts of complex peptide structure.
2Reliability
If SEVI peptide is used to enhance viral infection, then infection efficiency is improved, but stability deteriorates due to aggregation
Solution Approach 1:
The invention extracts the essential fibril-forming domain from the full-length SEVI peptide. By taking out only the critical amino acid residues (248-286) responsible for nanofibril formation and viral capture, the patent creates a stabilized core sequence that maintains infection-enhancing activity while reducing the propensity for unwanted aggregation and degradation.
Solution Approach 2:
The patent modifies the peptide sequence parameters by truncating it to a shorter length and potentially adjusting amino acid composition to optimize stability. These parameter changes reduce the peptide's susceptibility to aggregation while preserving the key structural features needed for forming stable nanofibrils that enhance viral infection.
3Stability of the object's composition
If longer peptide sequences like SEVI are used, then fibril formation capability is improved, but production cost and complexity increase
Solution Approach 1:
The patent segments the complex SEVI peptide sequence into a shorter, focused motif that contains only the essential residues for fibril formation. This segmentation simplifies the peptide from 39 amino acids to a more manageable sequence, reducing production complexity while maintaining the ability to self-assemble into functional nanofibrils.
Solution Approach 2:
The invention extracts the core fibril-forming domain from the full-length SEVI peptide, removing non-essential sequences that contribute to complexity without adding functional value. This extraction results in a streamlined peptide sequence that is easier and cheaper to produce while retaining the critical self-assembly properties needed for viral infection enhancement.
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 fibril peptide significantly enhances virus infection efficiency, comparable to or exceeding existing enhancers like Vectofusin-1, while maintaining low cytotoxicity and stability, making it a cost-effective alternative for gene transfer applications.
Implementation Method 1
The fibril peptide consists of a sequence of from 8 to 20 amino acids and wherein said fibril peptide comprises the amino acid sequence RTIFIISM or a sequence at least 75% identical thereto
Data Source
AI summary
The present invention relates to a fibril peptide consisting of a sequence of from 8 to 20 amino acids and wherein said fibril peptide comprises the amino acid sequence RTIFIISM or a sequence at least 75% identical thereto. The present invention further relates to a method of delivering a cargo comprised in a particle into a host cell, comprising a) contacting said host cell with said particle and with a fibril peptide according to any one of claims 1 to 8; and, thereby b) delivering said cargo into said host cell; and to uses, kits, and devices related thereto.