Host-Modifying CRISPR Arrays for Selective Microbiota Shaping
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Solution Overview
Problem
Existing technologies struggle to effectively inhibit bacterial population growth and alter the relative ratios of different bacterial species in mixed populations, particularly in environments such as human microbiota, livestock, and industrial systems, without causing unintended harm or resistance.
Innovation Solution
Utilizing a host modifying (HM) CRISPR/Cas system that harnesses wild-type endogenous Cas nuclease activity to target specific bacterial strains for growth inhibition or killing, while sparing others, by introducing engineered nucleic acid sequences that guide Cas nuclease to modify target sequences within the host cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional methods are used to inhibit bacterial population growth, then bacterial growth is suppressed, but unintended harm to beneficial bacteria and development of resistance occurs
Solution Approach 1:
The patent applies local quality by designing crRNA sequences that are specific to particular bacterial species or strains, enabling the CRISPR/Cas system to target only the harmful bacteria while leaving beneficial bacteria unaffected. Each crRNA is customized to match the unique genetic sequence of the target pathogen, creating a localized and precise inhibitory effect rather than broad-spectrum suppression.
Solution Approach 2:
The invention segments the bacterial population into targetable units by using species-specific or strain-specific genetic sequences as targets. By dividing the inhibition strategy into multiple specific crRNA targets rather than a single broad mechanism, the system can selectively eliminate harmful bacteria while preserving beneficial ones, thereby improving selectivity without causing unintended harm.
2Productivity
If broad-spectrum antibiotics are used to treat infections, then pathogenic bacteria are killed, but antibiotic resistance develops
Solution Approach 1:
The patent changes the fundamental parameter of treatment specificity by moving from non-specific antibiotic action to highly specific CRISPR-guided nuclease activity. The system uses programmable crRNA sequences to recognize and target specific genetic parameters of pathogenic bacteria, thereby maintaining high treatment efficacy while avoiding the selection pressure that leads to antibiotic resistance.
Solution Approach 2:
The invention substitutes the mechanical/chemical action of antibiotics with a programmable biological recognition system. Instead of relying on antibiotics that bind to conserved bacterial structures, the CRISPR/Cas system uses sequence-specific RNA-DNA hybridization to identify and destroy target bacteria, providing a more precise mechanism that reduces resistance development.
3Reliability
If CRISPR arrays are introduced into host cells to modify target sequences, then selective growth inhibition is achieved, but system complexity increases
Solution Approach 1:
The patent uses vectors as intermediary carriers to deliver CRISPR arrays into host cells. These vectors act as mediators that simplify the delivery process by packaging the CRISPR components in a manageable format, thereby reducing the practical complexity of system implementation while maintaining the selectivity benefits of CRISPR technology.
Solution Approach 2:
The invention employs universal vector systems that can deliver CRISPR arrays targeting different bacterial species through the same delivery mechanism. This multi-functional approach allows a single vector platform to handle various therapeutic targets, reducing the overall system complexity by avoiding the need for separate delivery systems for each application.
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
Achieves selective and efficient growth inhibition of specific bacterial species, up to 10-fold reduction in targeted bacterial populations, and alters the relative ratios of bacterial sub-populations, useful for treating infections, reducing antibiotic resistance, and controlling microbiologically influenced corrosion and biofouling.
Implementation Method 1
the CRISPR array comprises a guide RNA (gRNA) that is capable of hybridizing to a target sequence to guide Cas in the host cell to modify the target sequence
Data Source
AI summary
The invention relates to methods, uses, systems, arrays, engineered nucleotide sequences and vectors for inhibiting bacterial population growth or for altering the relative ratio of sub-populations of first and second bacteria in a mixed population of bacteria. The invention is particularly useful, for example, for treatment of microbes such as for environmental, medical, 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.