Antibiotic-Free Gene Therapy Vector VTvaf17 for Reduced Immune Response

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Solution Overview

Problem

Current gene therapy vectors face limitations due to the presence of antibiotic resistance genes, viral regulatory elements, and excessive length, which can lead to immune responses, integration risks, and reduced efficiency in delivering therapeutic genes for conditions like neurodegenerative and mental disorders.

Innovation Solution

Development of gene therapy DNA vectors, such as VTvaf17, that lack antibiotic resistance genes and viral regulatory elements, optimized for smaller size to enhance penetration and expression of BDNF, VEGFA, BFGF, NGF, GDNF, NT3, CNTF, and IGF1 genes in eukaryotic cells, using specific restriction sites and antibiotic-free production methods.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional gene therapy vectors are used, then therapeutic genes can be delivered to treat neurodegenerative and mental disorders, but the presence of antibiotic resistance genes and viral regulatory elements causes immune responses and integration risks

Engineering Contradiction:

Improvesafety of gene therapyVSAvoidimmune responses and integration risks

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent removes antibiotic resistance genes and viral regulatory elements from the gene therapy vector construct. The vector backbone is designed to exclude these harmful elements while maintaining essential features for gene expression and delivery, thereby eliminating the source of immune responses and integration risks

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent converts the potential harm of requiring selective markers during bacterial transformation into a benefit by using a selectable marker system that does not involve antibiotic resistance genes. The marker enables efficient vector production and selection while being safe for therapeutic use in humans

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

2Productivity

If gene therapy vectors contain all necessary regulatory elements and markers, then production and selection are facilitated, but the vector length increases reducing penetration efficiency

Engineering Contradiction:

Improvevector production efficiencyVSAvoidvector DNA length

Core Design Contradiction:

ProductivityVSLength of moving object

Solution Approach 1:

The patent extracts and removes unnecessary sequences from the vector, including antibiotic resistance genes and excessive regulatory elements. This reduces the overall vector length to optimize penetration efficiency into target cells while maintaining essential functionality through a streamlined minimal backbone

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent optimizes the vector by changing the length parameter to a smaller size that enhances cellular penetration. The vector is redesigned with a compact structure that maintains all necessary functional elements while minimizing non-essential sequences, directly improving delivery efficiency

Inventive Principle:

Principle #35Parameter changes

3Ease of manufacture

If antibiotic resistance genes are used for vector production, then selection of transformed bacteria is achieved, but antibiotic traces may remain in the final product

Engineering Contradiction:

Improvevector productionVSAvoidantibiotic traces in product

Core Design Contradiction:

Ease of manufactureVSLoss of substance

Solution Approach 1:

The patent removes antibiotic resistance genes from the vector construct entirely. Alternative selectable markers that do not encode antibiotic resistance are used during bacterial transformation, eliminating the source of antibiotic traces in the final therapeutic product while maintaining production efficiency

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs transient selectable markers during the production phase that do not need to be permanently retained in the therapeutic vector. These markers facilitate efficient bacterial selection during manufacturing but are eliminated from the final product, ensuring safety without compromising production ease

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Data Source

PatentUS20240325569A1Gene therapy DNA vector based on gene therapy DNA vector VTvaf17 carrying the therapeutic gene selected from the group of BDNF, VEGFA, BFGF, NGF, GDNF, NT3, CNTF, and IGF1 genes for increasing the expression level of these therapeutic genes, method of its production and use, Escherichia coli strain SCS110-AF/VTvaf17-BDNF, or Escherichia coli strain SCS110-AF/VTvaf17-VEGFA, or Escherichia coli strain SCS110-AF/VTvaf17-BFGF, or Escherichia coli strain SCS110-AF/VTvaf17-NGF, or Escherichia coli str

Publication Date: 2024.10.03 CELL & GENE THERAPY LTD

AI summary

The invention refers to genetic engineering and can be used in biotechnology, medicine, and agriculture for the manufacture of gene therapy products. Gene therapy DNA vector based on the gene therapy DNA vector VTvaf 17 carrying the therapeutic gene selected from the group of BDNF, VEGFA, BFGF, NGF, GDNF, NT3, CNTF, and IGF1 genes was constructed in order to increase the expression level of this therapeutic gene in humans and animals, while gene therapy DNA vector VTvaf17-BDNF, or VTvaf 17-VEGFA, or VTvaf17-BFGF, or VTvaf17-NGF, or VTvaf17-GDNF, or VTvaf17-NT3, or VTvaf17-CNTF, or VTvaf17-IGFl, has the nucleotide sequence SEQ ID No. 1, or SEQ ID No. 2, or SEQ ID No. 3, or SEQ ID No. 4, or SEQ ID No. 5, or SEQ ID No. 6, or SEQ ID No. 7, or SEQ ID No. 8, respectively.