Engineered Plasmodia for Therapeutic Protein Delivery
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Solution Overview
Problem
Current methods for treating malaria lack effective, non-pathogenic vectors for delivering therapeutic proteins, as pathogenic Plasmodia pose risks and existing vectors are inefficient for protein production and delivery.
Innovation Solution
Engineered Plasmodia with heterologous nucleic acid molecules encoding therapeutic proteins are developed, which are non-pathogenic, auxotrophic, and incapable of synthesizing isoprenoid precursors, allowing for safe and efficient production and delivery of therapeutic proteins by genetic modification and integration into specific genes within the Plasmodium genome.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If pathogenic Plasmodia are used as vectors for delivering therapeutic proteins, then protein production capability is improved, but safety and pathogenicity risks worsen
Solution Approach 1:
The patent uses pathogenic Plasmodium species (P. falciparum, P. vivax) as the basis for engineered vectors, converting their natural pathogenicity into a benefit by harnessing their efficient protein production and intracellular replication capabilities. Through genetic modification, the harmful pathogenic functions are eliminated while retaining the beneficial vector functions for therapeutic protein delivery
Solution Approach 2:
The patent extracts and eliminates the pathogenic functions from Plasmodium vectors through genetic modification, specifically removing virulence factors and pathogenicity-associated genes while retaining the essential vector functions for intracellular replication and protein production, thereby creating non-pathogenic engineered vectors
2Ease of operation
If existing vectors are used for protein production, then delivery capability is achieved, but production efficiency and efficacy worsen
Solution Approach 1:
The patent optimizes multiple parameters of the Plasmodium vector system including genome integration sites, promoter strength, codon optimization for heterologous gene expression, and cultivation conditions to maximize therapeutic protein production efficiency while maintaining delivery capability to target cells
Solution Approach 2:
The engineered Plasmodium vectors are designed to perform multiple functions simultaneously: intracellular replication for amplification, heterologous protein production for therapeutic output, and targeted delivery to host cells, making them more versatile than existing single-function vectors
3Productivity
If Plasmodium genome is modified to integrate heterologous nucleic acid molecules, then therapeutic protein expression is improved, but genetic stability and control worsen
Solution Approach 1:
The patent performs preliminary genetic engineering to create optimized integration sites and regulatory elements in the Plasmodium genome before introducing heterologous therapeutic genes, ensuring proper genomic integration, stable inheritance, and controlled expression of the therapeutic proteins throughout the parasite lifecycle
Data Source
AI summary
Provided herein are engineered Plasmodia comprising a heterologous nucleic acid molecule encoding a therapeutic protein and compositions (e.g., pharmaceutical compositions) comprising the same; as well as methods of making engineeredPlasmodia comprising a heterologous nucleic acid molecule encoding a therapeutic protein and compositions (e.g., pharmaceutical compositions) comprising the same. The engineered Plasmodia provided herein are useful e.g., in pharmaceutical compositions and methods of treating diseases.