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PETBioNewsNewsDiscovery of a tiny CRISPR protein perfect for human genome editing

BioNews

Discovery of a tiny CRISPR protein perfect for human genome editing

Published 24 July 2020 posted in News and appears in BioNews 1057

Author

Christina Burke

Image by Peter Artymiuk via the Wellcome Collection. Depicts the shadow of a DNA double helix, on a background that shows the fluorescent banding of the output from a DNA sequencing machine.
CC BY 4.0
Image by Peter Artymiuk via the Wellcome Collection. Depicts the shadow of a DNA double helix, on a background that shows the fluorescent banding of the sequencing output from an automated DNA sequencing machine.

An exceptionally small CRISPR-associated enzyme, which may significantly increase the efficacy of human genome editing, has been discovered by US researchers...

An exceptionally small CRISPR-associated enzyme, which may significantly increase the efficacy of human genome editing, has been discovered by US researchers.

The research team hope this new protein, termed Cas-Φ (Cas-phi), is 'a hypercompact addition to the genome editing toolbox', which may contribute towards using genome editing to treat diseases in patients.

Currently, using CRISPR/Cas technology for genome editing is limited by the difficulty of delivering large Cas proteins to cells. Professor Jennifer Doudna, CRISPR pioneer and joint lead author of the research group at the University of California, noted this challenge as 'really one of the most important bottlenecks to the field right now'. Referring to Cas-Φ, she added: 'We think this very tiny virus-encoded CRISPR/Cas system may be one way to break through that barrier.'

The study, published in the journal Science, tested the function of the recently discovered Cas-Φ protein on both human and plant cells in vitro. While other more common Cas proteins, such as Cas9, rely on accessory proteins to operate, the researchers found that Cas-Φ could perform all functions on its own. Professor Doudna remarked that Cas-Φ was 'actually very good at what it does, but it is a lot smaller, about half the size of Cas9'.

The CRISPR/Cas protein system is a method of immunity found naturally in bacteria and archaea, where Cas proteins cut and destroy invading genetic material from viruses. In order to do this, Cas proteins must bind segments of DNA (or in some cases RNA), which can be difficult to access. The research team found that due to its small size, Cas-Φ was able to access and cut more regions of human and plant genomes than other common Cas proteins.

Similarly, while most known Cas proteins preferentially cut single-stranded DNA, the team discovered that Cas-Φ cleaves double-stranded DNA like that found in human cells. These properties could make Cas-Φ a better alternative than other CRISPR/Cas systems currently used for genome editing of human and plant cells.

Research by colleagues at the University of California, led by Professor Jill Banfield, had previously identified Cas-Φ. The study, published in the journal Nature earlier this year, was the first evidence of Cas proteins existing within viruses rather than in bacteria or other single-celled organisms. The viruses are known as bacteriophages, and these origins may explain the unusual properties of Cas-Φ.

The authors of the current study commented that the properties of Cas-Φ 'highlight huge (bacterio)phages as an exciting forefront for discovery and biotechnological applications for human health.'

Sources and References

  • 17/07/2020
    Science
    CRISPR-Cas? from huge phages is a hypercompact genome editor
  • 16/07/2020
    Berkeley News
    Megaphages harbor mini-Cas proteins ideal for gene editing
  • 16/07/2020
    Fierce Biotech
    Doudna's team identifies new 'hypercompact' CRISPR enzyme
  • 17/07/2020
    Front Line Genomics
    Discovery of hypercompact Cas? protein sparks excitement in genetic engineering potential
  • 12/02/2020
    Nature
    Clades of huge phages from across Earth’s ecosystems
  • 16/07/2020
    Genetic Engineering and Biotechnology News
    Tiny Cas protein, huge gene editing potential... Thanks, megaphage!

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