Non-Pathogenic Bacteria for Oral PTD-Protein Brain Delivery
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Solution Overview
Problem
Current protein replacement therapies for monogenic diseases, particularly those affecting the brain, face challenges such as high production costs, protein instability, and the need for invasive administration methods, which are unsuitable for widespread application.
Innovation Solution
The use of genetically modified non-pathogenic bacteria, such as Lactococcus lactis, to produce and secrete TATk-fusion proteins that can cross the blood-brain barrier, enabling oral administration and in vivo production of therapeutic proteins for a wide spectrum of monogenic pathologies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional protein replacement therapy is used for monogenic diseases affecting the brain, then therapeutic proteins can be delivered to patients, but the proteins cannot effectively cross the blood-brain barrier and require invasive administration methods
Solution Approach 1:
The patent uses non-pathogenic bacteria as a living delivery vehicle (intermediary) to transport therapeutic proteins across the blood-brain barrier. The bacteria naturally traverse biological barriers and deliver the fused PTD-protein directly to target tissues, eliminating the need for invasive administration while maintaining therapeutic efficacy
Solution Approach 2:
The patent replaces mechanical/invasive delivery methods (injections, infusions) with a biological delivery system. Non-pathogenic bacteria naturally navigate through the digestive tract and bloodstream, using biological mechanisms rather than mechanical force to deliver proteins to the brain
2Quantity of substance
If traditional protein production systems are used for therapeutic proteins, then proteins can be produced, but production costs are high and protein stability is poor
Solution Approach 1:
The patent employs non-pathogenic bacteria as self-replicating production factories that generate therapeutic proteins in vivo. The bacteria contain genetic constructs for producing the desired proteins and automatically replicate and produce proteins within the patient's body, eliminating external production facilities and reducing costs
Solution Approach 2:
The patent pre-equips non-pathogenic bacteria with genetic constructs (plasmids or integrated genes) encoding the therapeutic proteins before administration. The bacteria arrive at the target site already prepared to produce the required proteins, eliminating the need for complex external production and purification processes
3Ease of operation
If non-pathogenic bacteria are used to produce and deliver PTD-fusion proteins in vivo, then oral administration and blood-brain barrier crossing are enabled, but the complexity of the delivery system increases
Solution Approach 1:
The patent uses non-pathogenic bacteria that perform multiple functions simultaneously: they serve as the delivery vehicle, the production factory, and the protection mechanism for therapeutic proteins. This multi-functionality simplifies the overall system despite the biological complexity, as one organism replaces multiple separate components
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach allows for effective and cost-efficient delivery of therapeutic proteins to the brain and other organs, overcoming the limitations of traditional protein replacement therapies by providing a feasible and safe treatment option for neurological disorders.
Implementation Method 1
by virtue of the presence of the transduction domain (PTD), can be conveyed first into the blood and subsequently to various organs, including the brain, by crossing the blood-brain barrier
Data Source
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AI summary
The present invention provides the use of non-pathogenic bacteria as microbial cell factories for the live production of secretable protein transduction domain (PTD)-fusion protein, which can be used as a protein replacement therapy for a wide spectrum of monogenic pathologies, including those affecting the brain.