Mutant VSVG Envelope for Complement-Resistant Vector Delivery

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Solution Overview

Problem

Existing VSVG-based vectors used in clinical therapies, such as CAR-T cell therapy, are inactivated by complement in the serum, preventing them from effectively reaching target cells via intravenous injection.

Innovation Solution

A mutant VSVG envelope glycoprotein with specific amino acid mutations that prevent complement inactivation and reduce receptor recognition, enhancing vector delivery efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If VSVG-based vectors are used for clinical therapy, then they can mediate complement inactivation, but they are inactivated by complement in the serum, preventing effective delivery to target cells

Engineering Contradiction:

Improvecomplement inactivation capabilityVSAvoiddelivery efficacy

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent applies parameter changes by mutating specific amino acid residues (positions 214, 352, 50, and/or 146) in the VSVG envelope glycoprotein to alter its interaction with complement components. These mutations change the biochemical parameters of the glycoprotein to prevent complement-mediated inactivation while preserving or enhancing delivery capability.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent converts the harmful effect of complement recognition into a benefit by using the complement system's own mechanisms against it. The mutated VSVG exploits complement component interactions in a controlled manner to achieve both protection from inactivation and enhanced cellular uptake, turning the previously harmful complement response into a beneficial delivery mechanism.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

2Adaptability or versatility

If VSVG envelope glycoprotein is used for vector delivery, then it can be recognized by receptors for targeted delivery, but it is inactivated by complement before reaching target cells

Engineering Contradiction:

Improvereceptor recognition capabilityVSAvoidsurvival in serum

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent applies local quality by making specific localized changes at critical amino acid positions (214, 352, 50, and/or 146) within the VSVG envelope glycoprotein structure. These localized mutations specifically affect complement interaction sites while preserving other functional regions responsible for receptor recognition and membrane fusion, allowing different parts of the protein to have different functional properties.

Inventive Principle:

Principle #3Local quality

Data Source

PatentEP4696704A1Mutant VSVG and targeting vector

Publication Date: 2026.02.18 SHENZHEN GENOCURY BIOTECH CO LTD

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AI summary

Provided are a mutant VSVG and a targeting vector, belonging to the field of vector delivery. An envelope glycoprotein of vesicular stomatitis virus having a first mutation and a second mutation is provided, the first mutation causes the envelope glycoprotein to be unable to mediate complement inactivation; and the second mutation weakens the ability of the envelope glycoprotein to be recognized by a receptor. A targeting vector is also provided, which comprises : a first molecule that binds to an endocytic receptor of a target cell and a second molecule that is non-complement inactivated and promotes the release of a substance carried by the targeting vector into the cytoplasm; the second molecule promotes the endosomal escape or lysosomal escape of the targeting vector and prevents the targeting vector from being inactivated by a complement.