Gorilla Adenovirus Hexon Hypervariable Regions for Gene Transduction

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current adenoviral vectors, particularly those based on human adenovirus type 5 (Ad5), face efficiency limitations in gene transduction due to pre-existing neutralizing antibodies in humans, which reduce their broad application as vaccine carriers and gene therapy tools.

Innovation Solution

Development of novel adenovirus strains with high immunogenicity and low pre-existing immunity, featuring specific amino acid sequences in hypervariable regions of the adenoviral capsid proteins, such as hexon, to create recombinant viruses, virus-like particles, and vectors that evade the immune system.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If human adenovirus type 5 (Ad5) based vectors are used for gene transduction, then high immunogenicity and efficient transduction are achieved, but pre-existing neutralizing antibodies in humans reduce transduction efficiency

Engineering Contradiction:

Improvegene transduction efficiencyVSAvoidpre-existing neutralizing antibodies

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies specific local regions (hypervariable regions HVR1-HVR7) of the adenoviral capsid proteins (hexon, fiber, penton) while maintaining the overall viral structure. By changing amino acid sequences in these specific local areas, the virus evades pre-existing neutralizing antibodies without losing transduction efficiency

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent changes physical-chemical parameters of the viral capsid proteins by introducing novel amino acid sequences in hypervariable regions. This alters the antigenic properties of the virus, making it unrecognized by pre-existing human antibodies while maintaining functional integrity for gene delivery

Inventive Principle:

Principle #35Parameter changes

2Reliability

If adenoviral vectors with high immunogenicity are used, then strong immune responses are elicited, but pre-existing immunity in the general population limits broad application

Engineering Contradiction:

Improveimmune response strengthVSAvoidbroad application scope

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

Instead of using conventional human adenovirus types that are well-known to the immune system, the patent inverts the approach by using gorilla adenovirus sequences for key capsid proteins. This creates a novel adenovirus that maintains immunogenicity while being unrecognized by human pre-existing immunity, thereby expanding broad applicability

Inventive Principle:

Principle #13The other way round (Inversion)

3Object-affected harmful factors

If novel adenovirus strains with modified capsid proteins are developed, then evasion of pre-existing neutralizing antibodies is achieved, but complexity of virus construction increases

Engineering Contradiction:

Improveneutralizing antibody recognitionVSAvoidvirus construction complexity

Core Design Contradiction:

Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent divides the adenovirus construction into modular segments: using gorilla adenovirus sequences for specific genes (L3 hexon, L5 fiber, L2 penton) while potentially retaining other human adenovirus components. This segmented approach allows systematic assembly of chimeric viruses with desired properties without requiring complete de novo construction

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS20240002879A1Gorilla adenovirus nucleic acid- and amino acid-sequences, vectors containing same, and uses thereof

Publication Date: 2024.01.04 REITHERA SRL

AI summary

The present invention relates to novel adenovirus strains with a high immunogenicity and very low pre-existing immunity in the general human population. The absence of detectable neutralizing antibodies is due to novel hypervariable regions in the adenoviral capsid protein hexon. The present invention provides nucleotide and amino acid sequences of these novel adenovirus strains, as well as recombinant viruses, virus-like particles and vectors based on these strains. Further provided are pharmaceutical compositions and medical uses in the therapy or prophylaxis of a disease, and methods for producing an adenovirus or virus-like particles utilizing the novel sequences, recombinant viruses, virus-like particles and vectors.