Embedded Target Genes in Fungal Clusters for Human Target Discovery

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

The challenge of identifying and targeting human proteins for therapeutic intervention is limited, with only about 2% of human proteins successfully targeted by approved drugs, and only 10-15% considered 'druggable', as highlighted by Dixon et al Curr. Opin. Chem. Biol. 13:549, 2009, and Stockwell Sci. Am 305:20, 2011.

Innovation Solution

The present disclosure identifies and characterizes 'embedded target genes' (ETaGs) within eukaryotic biosynthetic gene clusters, particularly fungal, which are homologs of human genes of therapeutic interest, and provides methods for querying and annotating these genes to develop modulators for human targets.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional drug discovery methods are used to identify human protein targets, then only a limited number of proteins (2%) can be successfully targeted by approved drugs, but the potential therapeutic coverage is severely restricted

Engineering Contradiction:

Improvenumber of successfully targeted human proteinsVSAvoidtherapeutic coverage of human proteome

Core Design Contradiction:

ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent transitions from studying human proteins directly to studying their evolutionary counterparts in fungal biosynthetic gene clusters. This dimensional shift allows identification of therapeutic targets through homologous relationships, expanding the druggable proteome from 2% to potentially much higher coverage by leveraging evolutionary conservation across species

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The method performs preliminary identification of embedded target genes within fungal biosynthetic gene clusters before actual drug development. By pre-characterizing these homologous genes and their relationships to human proteins, the approach prepares a pipeline of validated therapeutic targets that can be systematically developed into drugs

Inventive Principle:

Principle #10Preliminary action

2Adaptability or versatility

If only 10-15% of human proteins are considered 'druggable', then the majority of human proteins remain inaccessible to pharmacological intervention, but this limitation restricts therapeutic options for many diseases

Engineering Contradiction:

Improvedruggability of human proteinsVSAvoidnumber of available therapeutic targets

Core Design Contradiction:

Adaptability or versatilityVSProductivity

Solution Approach 1:

The patent uses fungal homologs as copies or proxies for human proteins. By studying the fungal embedded target genes that are homologous to human proteins, researchers can infer druggability characteristics without directly testing every human protein. This copying approach allows identification of druggable targets through evolutionary conservation

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The methodology applies universally across the entire human proteome by leveraging evolutionary homology. Instead of being limited to proteins with known druggability, the approach can evaluate any human protein by finding its fungal homolog in biosynthetic gene clusters, making the druggability assessment universally applicable

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Loss of information

If passenger genes in biosynthetic gene clusters are studied for self-protective functions, then understanding of microbial resistance mechanisms is improved, but the connection to human therapeutic targets remains unexplored

Engineering Contradiction:

Improveunderstanding of biosynthetic gene cluster functionsVSAvoidapplicability to human therapeutics

Core Design Contradiction:

Loss of informationVSEase of manufacture

Solution Approach 1:

Instead of viewing passenger genes solely as microbial self-protective elements, the patent inverts the perspective by treating them as evolutionary homologs of human therapeutic targets. This inversion transforms genes previously considered non-essential or parasitic into valuable resources for human drug discovery

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

Fungal biosynthetic gene clusters serve as an intermediary system between microbial genetics and human therapeutics. The embedded target genes within these clusters act as mediators, allowing indirect study of human protein targets through their fungal counterparts, thereby bridging the gap between microbial biology and human medicine

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20260011401A1Human Therapeutic Targets and Modulators Thereof

Publication Date: 2026.01.08 LIFEMINE THERAPEUTICS INC

AI summary

Among other things, the present disclosure provides technologies for efficient and effective identification of ETaGs, for example, from fungi genomes. In some embodiments, provided technologies are particularly useful for identifying mammalian targets of biosynthetic products of fungi. In some embodiments, provided technologies are particularly useful for identifying and/or prioritizing human targets for drug development. In some embodiments, provided technologies are particularly useful for developing modulators for human targets based on biosynthetic products of fungi.