Chimeric Antimicrobial Peptide-CRISPR Constructs for Sequence-Specific Pathogen Targeting
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Solution Overview
Problem
The increasing problem of antibiotic resistance and the broad-spectrum nature of antibiotics, which can harm beneficial bacteria and lead to infections by opportunistic pathogens like Clostridium difficile, necessitates the development of novel antimicrobial solutions that can target specific pathogens without affecting beneficial microorganisms.
Innovation Solution
A chimeric construct comprising a cell-penetrating peptide linked to a CRISPR RNA (crRNA) is used to selectively target and kill target bacterial or archaeal cells, sparing beneficial bacteria by utilizing CRISPR-Cas systems to cleave specific DNA sequences.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If broad-spectrum antibiotics are used to treat infections, then the ability to clear infections is improved, but beneficial bacteria are harmed and antibiotic resistance develops
Solution Approach 1:
The patent applies local quality by designing sequence-specific antimicrobials that target particular bacterial pathogens based on their unique genetic sequences, rather than using broad-spectrum antibiotics that affect all bacteria. The crRNA guides the Cas9 nuclease to specific protospacer sequences in the bacterial genome, enabling precise targeting of pathogenic bacteria while preserving beneficial microbiota.
Solution Approach 2:
The patent uses copying by creating synthetic crRNA molecules that contain copies of complementary sequences to target bacterial DNA. These crRNA copies are designed to be complementary to specific protospacer sequences in the bacterial genome, allowing the CRISPR-Cas9 system to recognize and cleave the target DNA through sequence complementarity without affecting other bacteria.
2Object-generated harmful factors
If sequence-specific antimicrobials are developed to target specific pathogens, then beneficial bacteria are spared, but the complexity of the antimicrobial system increases
Solution Approach 1:
The patent applies segmentation by dividing the antimicrobial system into distinct functional components: the CRISPR array containing multiple spacer sequences, the crRNA guide molecules, and the Cas9 nuclease enzyme. Each component has a specific function - the spacers provide sequence specificity, the crRNA delivers the guide sequence to the target, and Cas9 performs the cleavage action. This modular segmentation allows for programmable specificity while maintaining manageable system complexity.
Solution Approach 2:
The patent uses an intermediary approach by introducing crRNA molecules as mediators between the CRISPR-Cas9 system and the target bacterial DNA. The crRNA serves as a programmable guide that directs the Cas9 nuclease to specific protospacer sequences, enabling sequence-specific targeting without requiring direct modification of the bacterial genome or complex delivery mechanisms.
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 effectively kills target cells while sparing beneficial bacteria, reducing the risk of infections and antibiotic resistance, and can be used to treat bacterial infections and conditions by administering the chimeric construct to subjects in need.
Implementation Method 1
comprising a cell-penetrating peptide linked to a CRISPR RNA (crRNA)
Implementation Method 2
utilizing CRISPR-Cas systems to cleave specific DNA sequences
Data Source
AI summary
The invention relates to antimicrobial compositions comprising cell-penetrating peptides linked to CRISPR RNAs and methods for their use.