Loop-Modified Capsid Polypeptides for Targeted VLNP Drug Delivery
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Solution Overview
Problem
Current drug delivery systems face challenges in achieving targeted and selective delivery to specific cells or tissues, such as tumor cells, with high bioavailability and low toxicity, while existing VLNPs derived from mammalian viruses are prone to immune clearance and have limited applicability beyond vaccination.
Innovation Solution
Development of VLNPs derived from Alphatetraviridae, specifically modified in loop regions to incorporate targeting peptides and chemical compounds, allowing for targeted drug delivery to diseased cells with enhanced stability and reduced immune interaction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If VLNPs derived from mammalian viruses are used for drug delivery, then targeted delivery capability is achieved, but immune clearance increases and applicability is limited
Solution Approach 1:
Instead of using mammalian viruses for drug delivery, the patent inverts the approach by using insect viruses (Alphatetraviridae) as the viral platform. This inversion avoids the immune clearance problem associated with mammalian viruses while maintaining the ability to deliver therapeutic agents to target cells through the viral capsid structure.
Solution Approach 2:
The patent modifies the capsid protein sequence by introducing specific amino acid changes at defined positions (e.g., positions 310-318, 329-339, etc.) to create loop modification regions. These parameter changes in the protein sequence enable the VLNPs to incorporate targeting peptides and chemical compounds while maintaining structural integrity and reducing immune interaction.
2Device complexity
If conventional drug delivery systems are used, then system simplicity is maintained, but targeted delivery efficiency and bioavailability are insufficient
Solution Approach 1:
The viral capsid structure serves multiple functions simultaneously: it protects the therapeutic payload, mediates cellular uptake through endocytosis, and provides targeting capability through surface-modified loops. This multi-functionality achieves high targeted delivery efficiency without requiring complex system assembly, as the capsid inherently performs all necessary delivery functions.
3Ease of manufacture
If synthetic carriers are used for drug delivery, then production control is improved, but toxicity increases and delivery efficiency decreases
Solution Approach 1:
The patent uses biologically derived capsid proteins from insect viruses rather than synthetic materials. By modifying specific parameter regions (loop modification regions) of the capsid protein, the system achieves controlled production characteristics while eliminating the toxicity associated with synthetic carriers. The natural protein structure provides biocompatibility and reduces harmful effects.
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 modified VLNPs enable efficient, high-yield production and targeted delivery of therapeutic agents to specific cells, reducing off-target effects and immune clearance, thus improving therapeutic efficacy and safety.
Implementation Method 1
The capsid protein sequence... is derived from a family of VLNPs derived from Alphatetraviridae
Implementation Method 2
Viral envelope subunits or protomers can be bound by covalent interactions such as disulphide bonds or electron sharing, or non-covalent bonds such as hydrogen bonds, ionic interactions or Van der Waals forces
Implementation Method 3
the drug is protected by the 'delivery vehicle'
Implementation Method 4
incorporate targeting peptides and chemical compounds
Data Source
Figure 1A
Figure 1B
Figure 2A~2H
AI summary
The present invention discloses a polypeptide comprising a capsid protein sequence consisting of eight core regions and seven loop modification regions, wherein the eight core regions are defined, respectively, by amino acid positions M1 to S309, P319 to R328, T340 to T342, M349 to F352, W359 to F362, V368 to Q373, T383 to T387 and T392 to N644 in the amino acid sequence according to SEQ ID NO: 1, wherein the eight core regions of the capsid protein sequence have at least 70 % sequence identity to the eight core regions of the amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2 at least in the range from R32 to N570, wherein the seven loop modification regions are defined, respectively, by amino acid positions A310 to I318, H329 to I339, I343 to T348, D353 to E358, A363 to D367, T374 to A382, and A388 to V391 in the amino acid sequence according to SEQ ID NO: 1, wherein at least one loop modification region of the capsid protein sequence differs from the corresponding loop modification region of the amino acid sequences according to SEQ ID NO: 1 and SEQ ID NO: 2 at least in that the at least one loop modification region comprises - a peptide insert sequence comprising at least 3 amino acids, so that the at least one loop modification region of the capsid protein sequence is extended with respect to the corresponding loop modification region of the amino acid sequences according to SEQ ID NO: 1 and SEQ ID NO: 2 by said number of amino acids; and/or - a cysteine residue, and Virus-like Nanoparticles (VLNPs) comprising such polypeptides.