Cell Suspension Constriction for Nucleus Payload Delivery

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Solution Overview

Problem

Current methods for intracellular delivery of biomolecules, such as gene therapy, face challenges including non-specific molecule delivery, modification or damage to payloads, high cell death, and low throughput due to the large size of biomolecules like polypeptides and nucleic acids, which struggle to cross the cellular membrane effectively.

Innovation Solution

Passing a cell suspension through a plurality of constrictions allows payloads, including nucleic acids, polypeptides, and gene editing tools, to enter the cell and be delivered to the nucleus, enhancing delivery efficiency and specificity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If electrical fields, nanoparticles, or pore-forming chemicals are used for intracellular delivery, then delivery can be achieved, but non-specific molecule delivery, modification or damage to payloads, high cell death, and low throughput occur

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidcell death and payload damage

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses an intermediary mechanism (pore-forming peptides or other delivery vehicles) that mediates between the payload and cell membrane, enabling specific and efficient delivery while minimizing direct harmful interactions between the payload and cell structures

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes key parameters of the delivery system including pore size, peptide sequence, and delivery conditions to optimize for specific payload delivery while reducing non-specific effects and cell damage

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If existing delivery methods are used, then some delivery is achieved, but delivery to the nucleus specifically is insufficient

Engineering Contradiction:

Improvedelivery specificity to nucleusVSAvoidoverall delivery efficiency

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The patent segments the delivery process into distinct stages: initial cell entry through pore formation, cytoplasmic transit, and nuclear entry, with each stage optimized by specific design elements to achieve both efficiency and nuclear targeting

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent adds the dimension of nuclear targeting to conventional cytoplasmic delivery by incorporating nuclear localization signals or mechanisms that guide payloads from the cytoplasm into the nucleus

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

3Adaptability or versatility

If large biomolecule complexes are delivered, then gene therapy and genetic engineering are enabled, but the large size prevents ready crossing of cellular membrane

Engineering Contradiction:

Improvecapability for gene therapy and genetic engineeringVSAvoidmembrane crossing ability

Core Design Contradiction:

Adaptability or versatilityVSEase of operation

Solution Approach 1:

The patent employs pore-forming peptides and other intermediary structures that create temporary channels through the membrane, allowing large biomolecule complexes to pass through without requiring the complexes themselves to have membrane-crossing capabilities

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent uses flexible pore-forming structures that can accommodate and guide large payload complexes through the membrane barrier, with the pore structure adapting to the size and shape of the delivered cargo

Inventive Principle:

Principle #30Flexible shells and thin films

Data Source

PatentUS20240247285A1Methods for delivering genome editing molecules to the nucleus or cytosol of a cell and uses thereof

Publication Date: 2024.07.25 STEMCELL TECHNOLOGIES CANADA INC

AI summary

The present disclosure provides methods for delivering one or more payloads (e.g., gene-editing pay load) to a cell, wherein the method comprises passing a cell suspension comprising the cell and the pay load through one or more constrictions, wherein the one or more constrictions deform the cell, thereby causing a perturbation of the cell such that the one or more pay loads enters the cell.