Enucleated Cell Engineering to Avoid DNA Transfer in Therapy

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Solution Overview

Problem

Current cell-based therapies face challenges such as uncontrolled proliferation, limited engineering capability, inconsistent efficacy, poor quality control, and patient safety concerns due to cell heterogeneity and unwanted DNA transfer.

Innovation Solution

The development of bioengineered enucleated cells that are genetically modified to express therapeutic agents and immune modulators, designed to be safe and controllable, using methods like high-speed centrifugation to remove the nucleus and enable large-scale manufacturing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If cell-based therapies are used to treat diseases, then therapeutic potential is improved, but patient safety and control are worsened due to uncontrolled proliferation and DNA transfer risks

Engineering Contradiction:

Improvetherapeutic potentialVSAvoiduncontrolled proliferation and DNA transfer

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent removes the nucleus containing genomic DNA from the cell, extracting the harmful element (DNA that can transfer and cause uncontrolled proliferation) while retaining the cytoplasmic therapeutic functions. This enucleation process eliminates the risk of nuclear-encoded gene transfer to host cells while preserving the cell's ability to deliver therapeutic cargo.

Inventive Principle:

Principle #2Taking out (Extraction)

2Adaptability or versatility

If traditional cell-based therapies are administered, then immune responses can be modulated, but immune recognition and rejection are worsened due to HLA antigen expression

Engineering Contradiction:

Improveimmune modulation capabilityVSAvoidimmune recognition

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

By removing the nucleus that contains HLA genes, the patent eliminates the source of HLA antigens that trigger immune recognition. The enucleated cell can still modulate immune responses through cytoplasmic components and secreted factors without expressing surface HLA molecules that would mark it for immune destruction.

Inventive Principle:

Principle #2Taking out (Extraction)

3Adaptability or versatility

If cell heterogeneity is present in cell-based therapies, then biological diversity is improved, but manufacturing quality control and reproducibility are worsened

Engineering Contradiction:

Improvebiological diversityVSAvoidquality control and reproducibility

Core Design Contradiction:

Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The patent creates a homogeneous population of enucleated cells that all lack nuclei and HLA antigens, ensuring consistent immunological properties. This standardization eliminates variability in immune recognition and improves manufacturing reproducibility, while the cells retain their therapeutic functionality.

Inventive Principle:

Principle #33Homogeneity

4Adaptability or versatility

If nucleated cells are used for therapy, then genetic engineering capability is improved, but safety and control are worsened due to risk of nuclear DNA transfer

Engineering Contradiction:

Improvegenetic engineering capabilityVSAvoidnuclear-encoded gene transfer to host

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent removes the nucleus that contains the risk of DNA transfer, allowing the use of genetically engineered cytoplasmic components (such as mRNA, proteins, or other therapeutic cargo) without the safety concerns associated with nuclear DNA. This enables therapeutic genetic engineering while eliminating the harmful potential of nuclear-encoded gene transfer.

Inventive Principle:

Principle #2Taking out (Extraction)

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

Enucleated cells provide a safe and controllable platform for delivering therapeutic cargo, avoiding unwanted DNA transfer and ensuring precise lifespan, thus enhancing therapeutic efficacy and safety.

Implementation Method 1

enucleated cell genetically engineered to express at least one of an exogenous DNA molecule, an exogenous RNA molecule, an exogenous protein, or an exogenous peptide

Methodology Applied

Scientific EffectGenetic engineering:

Implementation Method 2

the exogenous protein comprises a cytokine, IL-12, calreticulin, phosphatidylysine, phagocytosis prey-binding domain, annexin 1, OX40/OC40L, 4-1BB, B7 family members

Methodology Applied

Scientific EffectCytokine expression:

Implementation Method 3

the enucleated cell is genetically engineered to deplete the enucleated cell of immune recognition molecules. In some embodiments, the immune recognition molecules comprise HLA antigens, proteoglycans, sugar moieties, embryonic antigens

Methodology Applied

Scientific EffectDepletion of immune recognition molecules:

Implementation Method 4

the enucleated cell is genetically engineered to express at least one exogenous protein. In some embodiments, the exogenous protein is a cell surface protein. In some embodiments, the exogenous protein is an immune activating protein

Methodology Applied

Scientific EffectProtein expression:

Data Source

PatentUS20260069630A1Methods and use for bioengineering enucleated cells

Publication Date: 2026.03.12 RGT UNIV OF CALIFORNIA

AI summary

Provided are methods for treating a disease using bioengineered enucleated cells. Also provided herein are compositions comprising enucleated cells, wherein the enucleated cells have been loaded with clinically relevant biomolecules.