A decade of discovery: CRISPR functions and applications

  title={A decade of discovery: CRISPR functions and applications},
  author={Rodolphe Barrangou and P. Horvath},
  journal={Nature Microbiology},
This year marks the tenth anniversary of the identification of the biological function of CRISPR–Cas as adaptive immune systems in bacteria. In just a decade, the characterization of CRISPR–Cas systems has established a novel means of adaptive immunity in bacteria and archaea and deepened our understanding of the interplay between prokaryotes and their environment, and CRISPR-based molecular machines have been repurposed to enable a genome editing revolution. Here, we look back on the… 
Structural insights into the inactivation of CRISPR-Cas systems by diverse anti-CRISPR proteins
The structures of several anti-CRISPR proteins have now been reported, and here it is discussed their structural features, with a particular emphasis on topology, to discover their similarities and differences.
CRISPR: a new principle of genome engineering linked to conceptual shifts in evolutionary biology
Analysis of the evolutionary connections of Cas proteins reveals multiple contributions of mobile genetic elements (MGE) to the origin of various components of CRISPR-Cas systems, furthermore, different biological systems that function by genome manipulation appear to have evolved convergently from unrelated MGE.
Advances in Engineering CRISPR-Cas9 as a Molecular Swiss Army Knife
A broad toolkit of CRISPR-Cas9-based systems now available for diverse genome-editing tasks is reviewed, providing an overview of their core molecular structure and mechanism and the design principles used to engineer their diverse functionalities.
Harnessing “A Billion Years of Experimentation”: The Ongoing Exploration and Exploitation of CRISPR–Cas Immune Systems
The remarkable diversity of CRISPR–Cas adaptive immune systems is explored, the molecular components that mediate nucleic acid targeting are described, and the use of these RNA-guided machines for biotechnology applications are outlined.
The CRISPR tool kit for genome editing and beyond
A brief history of gene-editing tools is presented and the wide range of CRISPR-based genome-targeting tools are described, to conclude with future directions and the broader impact ofCRISPR technologies.
CRISPR-Cas Targeting of Host Genes as an Antiviral Strategy
Recent progress of the CRISPR-Cas technology in editing host genes as an antiviral strategy is summarized.
Development of CRISPR-Cas systems for genome editing and beyond
  • F. Zhang
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    Quarterly Reviews of Biophysics
  • 2019
A personal perspective on the development of CRISPR-Cas9 for genome editing within the broader context of the field is provided and the work to discover novel Cas effectors and develop them into additional molecular tools is discussed.
CRISPRdisco: An Automated Pipeline for the Discovery and Analysis of CRISPR-Cas Systems
An automated pipeline is developed, named CRISprdisco (CRISPR discovery), to identify CRISPR repeats and cas genes in genome assemblies, determine type and subtype, and describe system completeness, and opens new avenues to enable classification within a complex nomenclature.


The Heroes of CRISPR
Advances in CRISPR-Cas9 genome engineering: lessons learned from RNA interference
How the history of RNAi can inform today's challenges in CRISPR-Cas9 genome engineering such as efficiency, specificity, high-throughput screening and delivery for in vivo and therapeutic applications is examined.
The Role of CRISPR-Cas Systems in Virulence of Pathogenic Bacteria
Recently reported cases of potential involvement of CRISPR-Cas systems in bacterial stress responses in general and bacterial virulence in particular are described.
Diversity and evolution of class 2 CRISPR–Cas systems
A comprehensive census of class 2 types and class 2 subtypes in complete and draft bacterial and archaeal genomes is presented, evolutionary scenarios for the independent origin of different class 2 CRISPR–Cas systems from mobile genetic elements are outlined, and an amended classification and nomenclature of CRISpr–Cas is proposed.
Evolution and classification of the CRISPR–Cas systems
An updated analysis of the evolutionary relationships between CRISPR–Cas systems and Cas proteins is provided and a 'polythetic' classification that integrates the phylogenies of the most common cas genes, the sequence and organization of theCRISPR repeats and the architecture of the CRISpr–cas loci is proposed.
Annotation and Classification of CRISPR-Cas Systems.
A multipronged approach has been developed that combines phylogenetic analysis of the conserved Cas proteins with comparison of gene repertoires and arrangements in CRISPR-Cas loci, leading to the current classification of CRISpr-Cas systems into three distinct types and ten subtypes for each of which signature genes have been identified.
An updated evolutionary classification of CRISPR–Cas systems
An approach combining the analysis of signature protein families and features of the architecture of cas loci that unambiguously partitions most CRISPR–cas loci into distinct classes, types and subtypes is presented.
The diversity-generating benefits of a prokaryotic adaptive immune system
It is proposed that the resulting short-lived nature of CRISPR-dependent bacteria–virus coevolution has provided strong selection for the evolution of sophisticated virus-encoded anti-CRISPR mechanisms.
New CRISPR-Cas systems from uncultivated microbes
A number of CRISPR–Cas systems, including the first reported Cas9 in the archaeal domain of life, are identified using genome-resolved metagenomics, enabling validation of robust in vivo RNA-guided DNA interference activity in Escherichia coli.
CRISPR-Cas immunity in prokaryotes
Immunization through spacer acquisition enables a unique form of evolution whereby a population not only rapidly acquires resistance to its predators but also passes this resistance mechanism vertically to its progeny.