Programmable Nuclease Therapy for Rapid Durable Microbial Killing
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Solution Overview
Problem
Current treatments for acute microbial infections such as septicemia, sepsis, and septic shock are inadequate in terms of rapidity and durability, and there is a need for effective treatments that do not compromise other medical therapies, particularly in cancer patients.
Innovation Solution
The use of programmable nucleases that target specific microbial genome sites for rapid and selective killing or growth reduction, utilizing CRISPR/Cas systems and guide RNAs to achieve substantial microbial reduction within minutes and maintain efficacy for several hours.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If conventional antibiotics are used to treat acute microbial infections, then the infection can be treated, but the treatment is not rapid enough and lacks durability
Solution Approach 1:
The patent replaces conventional antibiotic mechanisms (metabolic inhibition, cell wall synthesis disruption) with a physical mechanism - programmable nuclease cutting of microbial DNA. This substitution enables rapid double-strand breaks in essential genes, causing immediate microbial death within minutes while maintaining durable effects for hours, thus resolving the contradiction between speed and durability of treatment.
Solution Approach 2:
The patent changes the mechanism of action from chemical inhibition to physical DNA cleavage. By using programmable nucleases (such as Cas9, Cas13, or other CRISPR systems) guided by RNA molecules, the treatment achieves rapid and durable microbial killing. The nucleic acid guide sequences can be designed to target specific essential genes, ensuring both speed of action and lasting effect, thereby resolving the treatment duration contradiction.
2Reliability
If conventional antibiotics are used to treat infections, then microbial growth is inhibited, but the treatment may compromise other medical therapies
Solution Approach 1:
The patent applies local quality by using programmable nucleases with specific guide RNAs to target only essential genes in the pathogenic microbe. This targeted approach spares beneficial microbes and does not interfere with the patient's other medical therapies (such as chemotherapy or immunosuppressants), thereby maintaining compatibility with concurrent treatments while ensuring effective infection treatment.
Solution Approach 2:
By replacing conventional antibiotics with programmable nuclease-based treatment, the patent eliminates the conflict between infection treatment and other medical therapies. The nuclease mechanism acts directly on microbial DNA without affecting human cells or interacting with other medications, thus resolving the compatibility issue while maintaining treatment effectiveness.
3Loss of time
If rapid treatment is administered to treat acute infections, then the infection can be addressed quickly, but the treatment duration is limited
Solution Approach 1:
The patent substitutes conventional antibiotic mechanisms with programmable nuclease cutting, which achieves rapid microbial killing within minutes while maintaining durable effects for hours. The DNA cleavage mechanism causes immediate and lasting damage to essential microbial genes, resolving the contradiction between rapid action and prolonged effectiveness.
Solution Approach 2:
The patent ensures continuity of useful action by designing nuclease treatments that maintain effectiveness over extended periods. The programmable nucleases continue to exert their killing effect on microbial populations for several hours after initial administration, providing both rapid response and sustained treatment duration without requiring frequent dosing.
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
The method achieves rapid and durable microbial killing, reducing infections by several logs within minutes and maintaining effectiveness for up to 3 hours, while allowing concurrent administration of other therapies without interference.
Implementation Method 1
The invention relates to methods of treating or preventing microbial infections by using the action of programmable nuclease cutting of microbe genomes
Implementation Method 2
the nuclease is programmable to cut a target site comprised by the genomes of microbes that have infected the subject
Implementation Method 3
The nuclease is programmable with a guide RNA to cut a target site comprised by the genomes of the microbes
Data Source
AI summary
The invention provides methods for treating or preventing microbial (eg, bacterial) infections and means for performing these methods. In particular, treatment of infections requiring rapid and durable therapy is made possible, such as for treating acute conditions such as septicemia, sepsis, SIRS or septic shock. The invention is particularly useful, for example, for treatment of microbes such as for environmental, food and beverage use. The invention relates inter alia to methods of controlling microbiologically influenced corrosion (MIC) or biofouling of a substrate or fluid in an industrial or domestic system. The invention also useful for the treatment of pathogenic bacterial infections in subjects receiving a treatment for a disease or condition, such as a transplant or a treatment for cancer, a viral infection or an autoimmune disease.