Research Topic

The Use of CRISPR/Cas as a Tool to Study and Target Viruses

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Several genome editing technologies including zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN) and homing endonucleases have recently been developed and used as tools to study viruses, but also to target these pathogens. Among these technologies, the bacterial clustered ...

Several genome editing technologies including zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN) and homing endonucleases have recently been developed and used as tools to study viruses, but also to target these pathogens. Among these technologies, the bacterial clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system is now broadly used because of its activity, specificity, and flexibility. The CRISPR revolution represents one of the most exciting recent advances in the field of microbiology.
CRISPR/Cas was discovered in bacteria and archaea as a novel defense system against virus attacks by sensing and cleaving the nucleic acids of invading foreign genetic elements in a sequence-dependent manner. The CRISPR components were subsequently adapted for genome engineering in eukaryotic cells, where it has proven to be a very efficient tool to study biological processes. Functional genetic screens provide one example of how CRISPR-Cas techniques can be exploited to dissect virus replication mechanisms and to decipher virus-induced pathological processes.
CRISPR/Cas has also been harnessed to target human pathogenic viruses as an innovative antiviral approach. Many early successes have been reported in which CRISPR/Cas was used to inactivate DNA and subsequently RNA viruses in various in vitro, ex vivo and in vivo model systems. A popular first target has been HIV, of which the integrated DNA genome can be excised or mutated by CRISPR as gene-editor, but CRISPR can also be used as a gene-activation tool to activate HIV gene expression from latency to achieve a cure (“shock and kill” strategy).
Limitations of the CRISPR/Cas system have also been highlighted, including effective and safe delivery methods and potential off-target effects. The bacterial origin of CRISPR systems may also provoke an immune response that can neutralize the therapeutic effect over time. A new twist to the CRISPR story is that bacteriophages have evolved to express anti-CRISPR proteins. Such natural anti-CRISPR (Acr) molecules enable new strategies to fine-tune the activity of CRISPR-based genome-editing tools.

In this Research Topic, we seek Reviews, Mini-Reviews, and Original Research articles that discuss the latest developments at the interphase of the CRISPR-Cas and virology fields, both concerning basic studies and applied antiviral approaches. We will deal with CRISPR research on any virus type from human, but a prominent place is reserved for HIV because the bulk of early CRISPR work was devoted to this pathogen. We also welcome articles discussing strategies used by viruses to avoid the destruction of their genome by CRISPR technology.


Keywords: CRISPR/Cas, Virus, HIV, Excision, Inactivation


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