Type 1 Pilus ADAS for Stable Mammalian Cell Targeting

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

There is a need for delivery vectors capable of targeting mammalian cells and delivering biological agents, particularly those with tropism to modulate biological systems, as existing systems face challenges in consistent expression and efficiency of type 1 pilus-mediated targeting.

Innovation Solution

Development of achromosomal dynamic active systems (ADAS) derived from parent bacterial cells that constitutively express type 1 pilus (T1P), engineered to enhance T1P expression and stability, allowing for increased targeting and delivery of biological agents to mammalian cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If type 1 pilus (T1P) expression is induced in parent bacterial cells, then targeting capability to mammalian cells is improved, but expression consistency and stability deteriorate due to phase variation

Engineering Contradiction:

Improvetargeting capabilityVSAvoidexpression consistency

Core Design Contradiction:

Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The patent applies preliminary action by pre-modifying the fimS promoter in parent bacterial cells to lock it in the 'ON' orientation before ADAS formation. This ensures that when ADAS are generated from these engineered parent cells, they inherit constitutive T1P expression capability without undergoing phase variation, thus achieving both targeting capability and expression consistency

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent enables self-service by designing parent cells with locked-on fimS promoters that automatically maintain T1P expression without requiring external induction signals. The ADAS derived from these cells inherit this self-sustaining expression mechanism, eliminating the need for external control and ensuring stable, consistent T1P production

Inventive Principle:

Principle #25Self-service

2Productivity

If T1P expression is increased to enhance delivery efficiency, then biological agent delivery effectiveness is improved, but system complexity increases

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidsystem complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent extracts the complexity of T1P expression control from the ADAS system by pre-engineering parent cells with locked-on fimS promoters. This separates the complexity management to the parent cell generation stage, allowing ADAS to inherit high T1P expression capability without carrying the burden of complex regulation mechanisms

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies parameter changes by permanently altering the promoter state from inducible to constitutive through genetic modification of the fimS promoter. This parameter change in the parent cells translates to consistently high T1P expression levels in ADAS, improving delivery efficiency without adding operational complexity

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20250375386A1ADAS comprising type 1 pili

Publication Date: 2025.12.11 FLAGSHIP PIONEERING INNOVATIONS VI LLC

AI summary

Provided herein are achromosomal dynamic active systems comprising a Type 1 pilus (TIP) and methods of making and using the same.