CRISPR Microbiota Editing for Selective Bacterial Inhibition
Find Innovative SolutionsGenerate Solutions
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, without causing unintended harm or requiring genetic manipulation.
Innovation Solution
Utilizing a host modifying (HM) CRISPR/Cas system that harnesses wild-type endogenous Cas nuclease activity to selectively target and inhibit specific bacterial strains while sparing others, achieved through engineered CRISPR arrays and vectors that introduce guide RNAs to guide Cas nucleases to target sequences.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional methods are used to inhibit bacterial population growth, then some bacterial growth is inhibited, but non-specific inhibition occurs affecting multiple bacterial species and causing unintended harm
Solution Approach 1:
The CRISPR/Cas system employs highly specific guide RNAs that target unique sequences in the genome of specific bacterial species or strains. This local specificity ensures that only the intended target is inhibited while other bacterial species remain unaffected, resolving the contradiction between achieving inhibition and avoiding unintended harm.
Solution Approach 2:
The system divides the bacterial population into target and non-target groups through sequence-specific recognition. By segmenting the inhibition effect to only affect bacteria with the specific target sequence, the system achieves selective inhibition without broad-spectrum damage to the microbiota.
2Manufacturing precision
If genetic manipulation is used to alter bacterial populations, then precise control is achieved, but complexity of the system increases
Solution Approach 1:
The CRISPR/Cas system is delivered as a self-contained genetic module that autonomously performs target recognition and cleavage within the bacterial cell. The system uses the host's own cellular machinery to execute the inhibition, reducing the need for complex external manipulation apparatus while maintaining precision.
3Quantity of substance
If broad-spectrum antibiotics are used to reduce bacterial populations, then antibiotic-resistant bacteria are reduced, but disruption of microbiota balance occurs
Solution Approach 1:
The CRISPR/Cas system targets specific genetic sequences unique to pathogenic or antibiotic-resistant bacterial species while leaving commensal bacteria unaffected. This localized targeting preserves the overall microbiota composition and balance while selectively eliminating harmful bacteria, resolving the contradiction between reducing resistant bacteria and maintaining microbiota stability.
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 growth inhibition of specific bacterial species by at least 10-fold, allowing for targeted alteration of bacterial ratios in mixed populations, including human gut microbiota, and reducing antibiotic-resistant bacteria, while minimizing off-target effects.
Implementation Method 1
an extensively documented bacterial adaptive immune system is the CRISPR/Cas system
Implementation Method 2
engineered CRISPR arrays and vectors that introduce guide RNAs to guide Cas nucleases to target sequences
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.


