ArticleBiology direct2022
In silico optimization of RNA-protein interactions for CRISPR-Cas13-based antimicrobials.
Article in Biology direct, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 18 citations in OpenAlex.
- Molecular Docking as a Key Driver of Biocontrol for Agri-Food Security.Biotech (Basel (Switzerland)) · 2025Review
- And… cut! - how conformational regulation of CRISPR-Cas effectors directs nuclease activity.The Biochemical journal · 2025Review
- Self-assembling T7 phage syringes with modular genomes for targeted delivery of penicillin against β-lactam-resistant Escherichia coli.BMC biotechnology · 2025Article
- Developing a Versatile Arsenal: Novel Antimicrobials as Offensive Tools Against Pathogenic Bacteria.Microorganisms · 2025Review
- A New Insight into Phage Combination Therapeutic Approaches Against Drug-Resistant Mixed Bacterial Infections.PHAGE (New Rochelle, N.Y.) · 2024Review
- A pangenome analysis of ESKAPE bacteriophages: the underrepresentation may impact machine learning models.Frontiers in molecular biosciences · 2024Article
- CRISPR-Cas-Docker: web-based in silico docking and machine learning-based classification of crRNAs with Cas proteins.BMC bioinformatics · 2023Article
- Three Innovations of Next-Generation Antibiotics: Evolvability, Specificity, and Non-Immunogenicity.Antibiotics (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA-protein interactions are crucial for diverse biological processes. In prokaryotes, RNA-protein interactions enable adaptive immunity through CRISPR-Cas systems. These defence systems utilize CRISPR RNA (crRNA) templates acquired from past infections to destroy foreign genetic elements through crRNA-mediated nuclease activities of Cas proteins. Thanks to the programmability and specificity of CRISPR-Cas systems, CRISPR-based antimicrobials have the potential to be repurposed as new types of antibiotics. Unlike traditional antibiotics, these CRISPR-based antimicrobials can be designed to target specific bacteria and minimize detrimental effects on the human microbiome during antibacterial therapy. In this study, we explore the potential of CRISPR-based antimicrobials by optimizing the RNA-protein interactions of crRNAs and Cas13 proteins. CRISPR-Cas13 systems are unique as they degrade specific foreign RNAs using the crRNA template, which leads to non-specific RNase activities and cell cycle arrest. We show that a high proportion of the Cas13 systems have no colocalized CRISPR arrays, and the lack of direct association between crRNAs and Cas proteins may result in suboptimal RNA-protein interactions in the current tools. Here, we investigate the RNA-protein interactions of the Cas13-based systems by curating the validation dataset of Cas13 protein and CRISPR repeat pairs that are experimentally validated to interact, and the candidate dataset of CRISPR repeats that reside on the same genome as the currently known Cas13 proteins. To find optimal CRISPR-Cas13 interactions, we first validate the 3-D structure prediction of crRNAs based on their experimental structures. Next, we test a number of RNA-protein interaction programs to optimize the in silico docking of crRNAs with the Cas13 proteins. From this optimized pipeline, we find a number of candidate crRNAs that have comparable or better in silico docking with the Cas13 proteins of the current tools. This study fully automatizes the in silico optimization of RNA-protein interactions as an efficient preliminary step for designing effective CRISPR-Cas13-based antimicrobials.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.