BBB-Permeable Peptide Carrier for Large-Molecule Brain Delivery

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Solution Overview

Problem

Existing carrier molecules for delivering substances across the blood-brain barrier (BBB) face limitations in size and immunogenicity, hindering efficient delivery of water-soluble drugs and proteins to the brain.

Innovation Solution

A novel BBB permeable peptide with specific amino acid sequences, including SLSHSPQ (SEQ ID NO: 1) and variations, which can be cyclic or contain unnatural amino acids, is developed to facilitate BBB permeation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If monoclonal antibodies or cell membrane permeable peptides are used as BBB permeable carriers, then BBB permeability is improved, but the size of substance to be permeated is limited

Engineering Contradiction:

ImproveBBB permeabilityVSAvoidsize range of permeated substance

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The invention modifies the molecular weight parameter of the carrier by using a small peptide (7 amino acids: SLSHSPQ) instead of large monoclonal antibodies or larger peptides. This parameter change enables the carrier to penetrate the BBB effectively while accommodating larger cargo molecules up to 100 kDa or more, thus resolving the contradiction between BBB permeability and cargo size capacity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates a simplified version (peptide) that copies the essential function of larger carriers (monoclonal antibodies) for BBB permeation. The peptide SLSHSPQ replicates the BBB-penetrating capability without the size limitations, allowing it to serve as a versatile carrier for various sized substances including large molecules

Inventive Principle:

Principle #26Copying

2Reliability

If monoclonal antibodies are used as BBB permeable carriers, then BBB permeability is improved, but immunogenicity occurs

Engineering Contradiction:

ImproveBBB permeabilityVSAvoidimmunogenicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention replaces long-lived monoclonal antibodies with a short peptide sequence (SLSHSPQ) that performs the same BBB-penetration function temporarily. This disposable-like approach uses a minimal structure that achieves the desired effect without triggering immunogenic responses, eliminating the harmful effect while maintaining functionality

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The invention extracts only the essential BBB-penetrating functional sequence from larger immunogenic carriers like monoclonal antibodies. By isolating and optimizing this specific 7-amino acid sequence (SLSHSPQ), the invention retains the beneficial BBB permeability while removing the harmful immunogenic components present in full antibodies

Inventive Principle:

Principle #2Taking out (Extraction)

Data Source

PatentUS12384816B2Blood-brain barrier permeable peptide

Publication Date: 2025.08.12 NAT UNIV CORP KUMAMOTO UNIV

AI summary

The present invention has an object of providing a novel peptide that is permeable to the blood-brain barrier. The present invention provides a blood-brain barrier permeable peptide containing an amino acid sequence: SLSHSPQ (SEQ ID NO: 1) (where P may be substituted). The present invention also provides a carrier molecule for intracerebral delivery containing the peptide, a complex composed of the peptide and a target molecule that is allowed to permeate the blood-brain barrier, and a blood-brain barrier permeable composition containing the complex.