Anti-CRISPR proteins as a therapeutic agent against drug-resistant bacteria

Vyas, Pallavi; Mangesh, Harish

doi:10.1016/j.micres.2022.126963

Cited by 12 publications

(3 citation statements)

References 111 publications

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“…One approach to inhibiting Cas9 involves naturally occurring proteins from bacteriophages, developed as a counter to CRISPR systems [ 33 ]. Some of these, such as AcrIE1, have demonstrated the ability to block site-specific DNA cleavage [ 34 ]. However, therapeutic proteins come with significant drawbacks, including a short half-life, poor stability, low solubility, and high production costs [ 35 ].…”

Section: Crispr/cas9-mediated Genome Editingmentioning

confidence: 99%

Molecular Marvels: Small Molecules Paving the Way for Enhanced Gene Therapy

Hasselbeck,

Cheng

2023

Pharmaceuticals

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In the rapidly evolving landscape of genetic engineering, the advent of CRISPR-Cas technologies has catalyzed a paradigm shift, empowering scientists to manipulate the genetic code with unprecedented accuracy and efficiency. Despite the remarkable capabilities inherent to CRISPR-Cas systems, recent advancements have witnessed the integration of small molecules to augment their functionality, introducing new dimensions to the precision and versatility of gene editing applications. This review delves into the synergy between CRISPR-Cas technologies based specifically on Cas9 and small-molecule drugs, elucidating the pivotal role of chemicals in optimizing target specificity and editing efficiency. By examining a diverse array of applications, ranging from therapeutic interventions to agricultural advancements, we explore how the judicious use of chemicals enhances the precision of CRISPR-Cas9-mediated genetic modifications. In this review, we emphasize the significance of small-molecule drugs in fine-tuning the CRISPR-Cas9 machinery, which allows researchers to exert meticulous control over the editing process. We delve into the mechanisms through which these chemicals bolster target specificity, mitigate off-target effects, and contribute to the overall refinement of gene editing outcomes. Additionally, we discuss the potential of chemical integration in expanding the scope of CRISPR-Cas9 technologies, enabling tailored solutions for diverse genetic manipulation challenges. As CRISPR-Cas9 technologies continue to evolve, the integration of small-molecule drugs emerges as a crucial avenue for advancing the precision and applicability of gene editing techniques. This review not only synthesizes current knowledge but also highlights future prospects, paving the way for a deeper understanding of the synergistic interplay between CRISPR-Cas9 systems and chemical modulators in the pursuit of more controlled and efficient genetic modifications.

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Section: Crispr/cas9-mediated Genome Editingmentioning

confidence: 99%

Molecular Marvels: Small Molecules Paving the Way for Enhanced Gene Therapy

Hasselbeck,

Cheng

2023

Pharmaceuticals

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“…In addition to acting as a safety measure to control genome editing, Acr molecules could be used as antibiotics against drug-resistant bacteria [ 48 , 49 ]. Thus, many more small-molecule inhibitors against Cas nucleases are expected in the near future, with the concomitant development of high-through assays suitable for each nuclease [ 50 ].…”

Section: Small-molecule Control Of Cas Nucleasesmentioning

confidence: 99%

Small Molecules for Enhancing the Precision and Safety of Genome Editing

2022

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Clustered regularly interspaced short palindromic repeats (CRISPR)-based genome-editing technologies have revolutionized biology, biotechnology, and medicine, and have spurred the development of new therapeutic modalities. However, there remain several barriers to the safe use of CRISPR technologies, such as unintended off-target DNA cleavages. Small molecules are important resources to solve these problems, given their facile delivery and fast action to enable temporal control of the CRISPR systems. Here, we provide a comprehensive overview of small molecules that can precisely modulate CRISPR-associated (Cas) nucleases and guide RNAs (gRNAs). We also discuss the small-molecule control of emerging genome editors (e.g., base editors) and anti-CRISPR proteins. These molecules could be used for the precise investigation of biological systems and the development of safer therapeutic modalities.

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“…The overuse of antimicrobial drugs in agriculture and medicine in recent decades has led to the emergence of multi-drug-resistant (MDR) Salmonella ( 9 – 11 ). S .…”

Section: Introductionmentioning

confidence: 99%

Efficient screening of adsorbed receptors for Salmonella phage LP31 and identification of receptor-binding protein

Ge,

Ye,

Cai

et al. 2023

Microbiol Spectr

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The adsorption process is the first step in the lifecycle of phages and plays a decisive role in the entire infection process. Identifying the adsorption mechanism of phages not only makes phage therapy more precise and efficient but also enables the exploration of other potential applications and modifications of phages. Phage LP31 can lyse multiple Salmonella serotypes, efficiently clearing biofilms formed by Salmonella enterica serovar Enteritidis ( S . Enteritidis) and significantly reducing the concentration of S . Enteritidis in chicken feces. Therefore, LP31 has great potential for many practical applications. In this study, we established an efficient screening method for phage infection-related genes and identified a total of 10 genes related to the adsorption process of phage LP31. After the construction of strain C50041Δ rfaL 58−358 , it was found that the knockout strain had a rough phenotype as an O-antigen-deficient strain. Adsorption rate and transmission electron microscopy experiments showed that the receptor for phage LP31 was the O 9 antigen of S . Enteritidis. Homology comparison and adsorption experiments confirmed that the tail fiber protein Lp35 of phage LP31 participated in the adsorption process as a receptor-binding protein. IMPORTANCE A full understanding of the interaction between phages and their receptors can help with the development of phage-related products. Phages like LP31 with the tail fiber protein Lp35, or a closely related protein, have been reported to effectively recognize and infect multiple Salmonella serotypes. However, the role of these proteins in phage infection has not been previously described. In this study, we established an efficient screening method to detect phage adsorption to host receptors. We found that phage LP31 can utilize its tail fiber protein Lp35 to adsorb to the O 9 antigen of S. Enteritidis, initiating the infection process. This study provides a great model system for further studies of how a phage-encoded receptor-binding protein (RBP) interacts with its host's RBP binding target, and this new model offers opportunities for further theoretical and experimental studies to understand the infection mechanism of phages.

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Anti-CRISPR proteins as a therapeutic agent against drug-resistant bacteria

Cited by 12 publications

References 111 publications

Molecular Marvels: Small Molecules Paving the Way for Enhanced Gene Therapy

Molecular Marvels: Small Molecules Paving the Way for Enhanced Gene Therapy

Small Molecules for Enhancing the Precision and Safety of Genome Editing

Efficient screening of adsorbed receptors for Salmonella phage LP31 and identification of receptor-binding protein

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