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Discovery of a tiny CRISPR protein perfect for human genome editing

27 July 2020
Appeared in BioNews 1057

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