Engineered Candida albicans Strains Expressing Cytokines

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Solution Overview

Problem

Current treatments for candidiasis, particularly oropharyngeal candidiasis, lack effective vaccines and are limited by drug resistance and toxicity, with no available vaccines for fungal species, highlighting the need for alternative preventive strategies.

Innovation Solution

Genetically modified Candida albicans strains engineered to express cytokines or chemokines such as IL-17A, CXCL1, CXCL2, and CXCL5, which are administered to induce immune responses and prevent or limit candidiasis by recruiting neutrophils and enhancing immunity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If genetically modified C. albicans strains expressing cytokines or chemokines are administered, then immune response and neutrophil recruitment are enhanced to prevent candidiasis, but the complexity of the treatment approach increases

Engineering Contradiction:

Improveprevention of candidiasisVSAvoidtreatment approach complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The engineered C. albicans strain serves itself by expressing cytokines (IL-17A, IL-8) and chemokines (CXCL1, CXCL2, CXCL5) that recruit neutrophils to clear the infection, turning the pathogen into its own therapeutic agent against candidiasis

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

Cytokines and chemokines act as intermediary molecules that bridge the engineered C. albicans strain and the host immune system, mediating the recruitment of neutrophils and enhancement of immune response to prevent candidiasis

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If current antifungal treatments are used, then candidiasis can be treated, but drug resistance and toxicity limit their effectiveness

Engineering Contradiction:

Improvetreatment effectivenessVSAvoiddrug resistance and toxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful presence of C. albicans into a beneficial therapeutic effect by engineering the strain to express immune-modulating cytokines and chemokines that actively prevent candidiasis, transforming a pathogen into a protective probiotic

Inventive Principle:

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

Data Source

PatentUS10160974B2Engineered cytokine- and chemokine-expressing <i>Candida albicans </i>strains and methods of use

Publication Date: 2018.12.25 CARNEGIE MELLON UNIV

AI summary

Recombinant nucleic acid constructs for expression of heterologous cytokines or chemokines in C. albicans, and genetically modified C. albicans strains comprising the recombinant nucleic acid constructs, are described. The recombinant nucleic acid molecules include a C. albicans gene promoter sequence, a nucleic acid sequence encoding a C. albicans secreted protein signal sequence and a heterologous open reading frame (ORF) of a cytokine or chemokine gene. Also described are a method of expressing a heterologous cytokine or chemokine protein in a subject, and a method of treating or inhibiting the development of candidiasis in a subject. These methods include administering a genetically modified C. albicans containing a recombinant nucleic acid construct for expression of a heterologous cytokine or chemokine. Exemplary cytokines or chemokines include IL8, IL17A, CXCL1, CXCL2 and CXCL5.