T4 Phage Packaging Machine for Dual Gene and Protein Delivery

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Solution Overview

Problem

Current methods lack efficient platforms for delivering both genes and proteins into target cells, which is crucial for understanding genetic and infectious diseases such as cancer and AIDS, and for developing novel biomedical therapies.

Innovation Solution

A phage T4 DNA packaging machine is created by mixing a Soc-Hoc phage T4 head with a gp17 packaging motor, ATP, and DNA, then exposing it to Hoc and Soc fusion proteins, including a dendritic cell-specific ligand, to form a functional delivery vehicle that can package DNA and display proteins on its surface for targeted cell entry.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If current delivery platforms are used, then single gene or protein delivery is achieved, but simultaneous delivery of both genes and proteins into target cells is not possible

Engineering Contradiction:
Improvedelivery capabilityVSAvoiddelivery system complexity
Core Design Contradiction:
Adaptability or versatilityVSWeight of moving object

Solution Approach 1:

The patent merges gene delivery and protein delivery capabilities into a single bacteriophage T4-based platform. The phage capsid is engineered to simultaneously encapsidate DNA molecules and display functional proteins on its surface, enabling dual delivery functionality that overcomes the limitation of existing single-function platforms.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The bacteriophage T4 delivery platform is designed as a universal system that can deliver multiple types of cargo (genes and proteins) to multiple target cell types. The modular design allows different DNA molecules and proteins to be combined on the same phage particle, creating a multi-functional delivery vehicle applicable to various therapeutic scenarios.

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Reliability

If efficient gene and protein delivery is achieved, then therapeutic efficacy is improved, but delivery system complexity increases

Engineering Contradiction:
Improvedelivery efficiencyVSAvoidpackaging machine structure
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The bacteriophage T4 capsid serves as an intermediary structure that facilitates the delivery of both genes and proteins. By using the natural phage assembly machinery and structural components, the system achieves efficient co-delivery without requiring entirely new complex delivery devices, thus balancing efficacy with manageable complexity.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The delivery system employs a composite structure combining viral capsid proteins (for protection and targeting), packaged DNA (for genetic therapy), and displayed functional proteins (for immediate therapeutic effect). This composite approach enables simultaneous delivery of multiple therapeutic agents while leveraging the natural compatibility of these components.

Inventive Principle:
Principle #40Composite materials

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

This system achieves high-efficiency delivery of genes and proteins into mammalian cells, including dendritic cells, with the ability to elicit robust immune responses and potentially lead to new vaccine and genetic therapies.

Implementation Method 1

mixing a Soc- in vitro to package the one or more DNA molecules into the Soc-

Methodology Applied
Scientific EffectATP hydrolysis:

Data Source

PatentEP2964770B1In vitro and in vivo delivery of genes and proteins using the bacteriophage t4 DNA packaging machine
Publication Date: 2017.06.14 CATHOLIC UNIV OF AMERICA
  • EP2964770B1 patent drawingFigure 1
  • EP2964770B1 patent drawingFigure 2
  • EP2964770B1 patent drawingFigure 3~4

AI summary

Described is T4 DNA packaging machine comprising: one or more DNA molecules packaged in a head of the T4 DNA packaging machine, one or more Hoc-fused proteins displayed on the head of the T4 DNA packaging machine, and one or more Soc-fused proteins displayed on the head of the T4 DNA packaging machine. Also described are methods of making and using such a T4 DNA packaging machine.