Advancing the design and delivery of CRISPR antimicrobials

Fagen, Jennie R.; Collias, Daphne; Singh, Atul K.; Beisel, Chase L.

doi:10.1016/j.cobme.2017.10.001

Cited by 26 publications

(15 citation statements)

References 46 publications

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“…However, the delivery of the antimicrobial CRISPR-Cas system to the target bacteria is another key challenge. Most of the functional CRISPR-Cas-based antimicrobial systems developed to date are encoded on phage genomes [ 238 , 241 , 242 ], which is a typical combined usage of phages and phage-derived technologies. The development of programmable CRISPR-based antimicrobial platforms for multiple targeting and more efficient delivery may be essential strategies to overcome problems such as off-target effects and indiscriminate killing of bacteria.…”

Section: Rna-based Technology Modeled On Phage-bacterial Interactionsmentioning

confidence: 99%

Applications of phage-derived RNA-based technologies in synthetic biology

Zhang

2020

Synthetic and Systems Biotechnology

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As the most abundant biological entities with incredible diversity, bacteriophages (also known as phages) have been recognized as an important source of molecular machines for the development of genetic-engineering tools. At the same time, phages are crucial for establishing and improving basic theories of molecular biology. Studies on phages provide rich sources of essential elements for synthetic circuit design as well as powerful support for the improvement of directed evolution platforms. Therefore, phages play a vital role in the development of new technologies and central scientific concepts. After the RNA world hypothesis was proposed and developed, novel biological functions of RNA continue to be discovered. RNA and its related elements are widely used in many fields such as metabolic engineering and medical diagnosis, and their versatility led to a major role of RNA in synthetic biology. Further development of RNA-based technologies will advance synthetic biological tools as well as provide verification of the RNA world hypothesis. Most synthetic biology efforts are based on reconstructing existing biological systems, understanding fundamental biological processes, and developing new technologies. RNA-based technologies derived from phages will offer abundant sources for synthetic biological components. Moreover, phages as well as RNA have high impact on biological evolution, which is pivotal for understanding the origin of life, building artificial life-forms, and precisely reprogramming biological systems. This review discusses phage-derived RNA-based technologies terms of phage components, the phage lifecycle, and interactions between phages and bacteria. The significance of RNA-based technology derived from phages for synthetic biology and for understanding the earliest stages of biological evolution will be highlighted.

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Section: Rna-based Technology Modeled On Phage-bacterial Interactionsmentioning

confidence: 99%

Applications of phage-derived RNA-based technologies in synthetic biology

Zhang

2020

Synthetic and Systems Biotechnology

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“…In addition, the transfer of the undesired phenotypic traits is abolished among strains infected by the delivery bacteriophage. Many groups are studying this strategy (for review see Fagen et al 2017 [ 48 ]), with several start-ups (Locus in US, Nemesis in UK or Eligo in France) already developing such a bacteriophage for commercial use. Still, classic problems of bacteriophage therapy, such as finding suitable bacteriophages for each individual pathogenic strain or the potential immune reaction of the body to large doses of bacteriophage virions, remain obstacles for application.…”

Section: Limitations and Concerns For Crispr/cas Gene Edited Bactementioning

confidence: 99%

Silk Route to the Acceptance and Re-Implementation of Bacteriophage Therapy—Part II

et al. 2018

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This perspective paper follows up on earlier communications on bacteriophage therapy that we wrote as a multidisciplinary and intercontinental expert-panel when we first met at a bacteriophage conference hosted by the Eliava Institute in Tbilisi, Georgia in 2015. In the context of a society that is confronted with an ever-increasing number of antibiotic-resistant bacteria, we build on the previously made recommendations and specifically address how the Nagoya Protocol might impact the further development of bacteriophage therapy. By reviewing a number of recently conducted case studies with bacteriophages involving patients with bacterial infections that could no longer be successfully treated by regular antibiotic therapy, we again stress the urgency and significance of the development of international guidelines and frameworks that might facilitate the legal and effective application of bacteriophage therapy by physicians and the receiving patients. Additionally, we list and comment on several recently started and ongoing clinical studies, including highly desired double-blind placebo-controlled randomized clinical trials. We conclude with an outlook on how recently developed DNA editing technologies are expected to further control and enhance the efficient application of bacteriophages.

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“…Interestingly, a study demonstrated that the use of carbapenems caused more endotoxins than phages [ 80 ]; emerging alternatives to circumvent this issue include engineering lysis-deficient phages [ 81 ]. For CRISPR/Cas9, some concerns, including off-target gene targeting and escape rates, are summarised in a review, along with recent works [ 77 , 82 , 83 ]. These concerns can be addressed progressively as areas in CRISPR/Cas9 research, such as optimising gene multiplexing and continuing the development of increased specificity and efficiency of CRISPR/Cas9 in target organisms.…”

Section: Phage-mediated Modulation Of Gut Microbiomementioning

confidence: 99%

Targeted Approaches for In Situ Gut Microbiome Manipulation

Lee

Shen

Hwang

et al. 2018

Genes

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Microbial communities and their collective genomes form the gut microbiome, of which bacteria are the major contributor. Through their secreted metabolites, bacteria interact with the host, influencing human health and physiology. Perturbation of the microbiota and metabolome has been associated with various diseases and metabolic conditions. As knowledge on fundamental host-microbiome interactions and genetic engineering tools becomes readily available, targeted manipulation of the gut microbiome for therapeutic applications gains favourable attention. Manipulation of the gut microbiome can be achieved by altering the microbiota population and composition, or by modifying the functional metabolic activity of the microbiome to promote health and restore the microbiome balance. In this article, we review current works that demonstrate various strategies employed to manipulate the gut microbiome in situ to various degrees of precision.

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Advancing the design and delivery of CRISPR antimicrobials

Cited by 26 publications

References 46 publications

Applications of phage-derived RNA-based technologies in synthetic biology

Applications of phage-derived RNA-based technologies in synthetic biology

Silk Route to the Acceptance and Re-Implementation of Bacteriophage Therapy—Part II

Targeted Approaches for In Situ Gut Microbiome Manipulation

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