Dual Vector System for Co-Delivery of Split Activator Receptors

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current genetic vector systems often fail to deliver large polynucleotide sequences efficiently to cells, leading to heterogeneity in cell populations where some cells receive only one of two required polynucleotides, necessitating a mechanism to ensure both polynucleotides are delivered to the same target cell.

Innovation Solution

A dual vector system is introduced, where one vector encodes a first part of an activator receptor and another vector encodes a second part, requiring both vectors to be taken up by a cell to form a functional activator receptor, thereby ensuring co-expression and reducing heterogeneity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a single vector delivers one polynucleotide sequence, then the delivery process is simple, but cells may stochastically receive only one of two required polynucleotides leading to heterogeneity

Engineering Contradiction:

Improveco-delivery of two polynucleotides to same cellVSAvoiddual vector system structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The activator receptor is divided into two separate polynucleotide sequences, each delivered by a different vector. This segmentation ensures that cells must receive both vectors to express the complete functional receptor, thereby guaranteeing co-delivery while maintaining manageable vector sizes and complexity

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

A control mechanism is introduced where an inhibitory receptor (delivered by one vector) and a split activator receptor (delivered by two vectors) interact within the cell. The inhibitory receptor blocks activator function unless both polynucleotides are present, serving as an intermediary control that enforces co-delivery without requiring complex vector design

Inventive Principle:

Principle #24Intermediary (Mediator)

2Quantity of substance

If vectors are made smaller for easier delivery, then delivery efficiency improves, but the ability to deliver large polynucleotide sequences is reduced

Engineering Contradiction:

Improvepolynucleotide sequence sizeVSAvoiddelivery efficiency

Core Design Contradiction:

Quantity of substanceVSProductivity

Solution Approach 1:

Large polynucleotide sequences are segmented into smaller units that can be accommodated by individual vectors with optimized delivery characteristics. The segmented sequences are then reassembled in the target cell to form the complete functional receptor, thereby achieving both efficient delivery and delivery of large sequences

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent employs a nested structure where multiple functional elements (inhibitory receptor, split activator parts, control mechanisms) are organized across two vectors. This nesting allows complex functionality to be delivered through manageable vector units that can be efficiently transduced

Inventive Principle:

Principle #7Nested doll (Nesting)

Data Source

PatentUS20240335471A1Vector systems for delivery of two polynucleotides and methods of making and using same

Publication Date: 2024.10.10 A2 BIOTHERAPEUTICS INC

AI summary

The disclosure relates to a dual vector system with a first vector comprising a sequence encoding an inhibitory receptor and a sequence encoding a first part of an activator receptor; and a second vector, comprising a sequence encoding a second part of the activator receptor.