CRISPR, Megaphages harbor mini-Cas proteins ideal for gene editing (and gene therapy)

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phage
[ feyj ]
noun
bacteriophage.

bacteriophage
[ bak-teer-ee-uh-feyj ]
noun
any of a group of viruses that infect specific bacteria, usually causing their disintegration or dissolution.
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Now its been found that phages have a mini-Cas protein, a more compact form of CRISPR. This is useful for gene therapy... (viruses are used to get genes into the required cells)

Another issue is that the CRISPR-Cas system is rather large. The preferred method for ferrying it into the target organism and its cells are deactivated adeno-associated viruses (AAV’s). Think of a virus particle emptied out and refurbished as truck. Those viral trucks, however, are not that big. With a CRISPR-Cas in there, it gets crowded real quick.

But with this mini-Cas

This bacteriophage CRISPR system has a smaller, multi-functional Cas protein (about half the size of Cas9), dubbed CasΦ (the Greek letter ‘phi’, also used as abbreviation for bacteriophage).

In other words, more room in the AAV truck, which means easier delivery and room for additional tools such as DNA templates to fix the DNA ‘cuts’ with a specified sequence.

https://medium.com/predict/tiny-gene-editing-tool-is-a-big-crispr-update-f4e9cdb142c7

One of the universities involved is, University of Berkeley , this is how they described the story...

The DNA-cutting proteins central to CRISPR-Cas9 and related gene-editing tools originally came from bacteria, but a newfound variety of Cas proteins apparently evolved in viruses that infect bacteria.

The new Cas proteins were found in the largest known bacteria-infecting viruses, called bacteriophages, and are the most compact working Cas variants yet discovered — half the size of today’s workhorse, Cas9.

Smaller and more compact Cas proteins are easier to ferry into cells to do genome editing, since they can be packed into small delivery vehicles, including one of the most popular: a deactivated virus called adeno-associated virus (AAV). Hypercompact Cas proteins also leave space inside AAV for additional cargo.

Megaphages harbor mini-Cas proteins ideal for gene editing - Berkeley News

A hypercompact Cas protein similar to CRISPR-Cas9, the revolutionary gene-editing tool, should allow easier viral delivery for gene therapy in humans and crops

news.berkeley.edu

 

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Short vid explaining CRISPR, Clustered Regularly Interspaced Short Palindromic Repeats.

 

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14 minute audio explaining how crispr was discovered and what it be might be used for..

The Genius of Accidents - Series 1 - CRISPR - BBC Sounds

A story of the discovery of genetic scissors that accidentally enabled fast gene editing.

www.bbc.co.uk

 

[alsoknownas]

My understanding (possibly flawed!) of CRISPR is that the 'genetic tech' was adapted as a self-regulatory system for bacteria to help repair their own DNA. This sounds like a virus has mimicked or hijacked that mechanism to insert it's own * ahem* remix versions into bacteria DNA sequences. presumably there may even be some back and forth as the various CRISPRs (I know they're not called CRISPRs - that's the human-derived gene technology and it's applications, right?) compete with each other to edit the genome, like zealot historians writing and re-writing history.

1) Is that anywhere near correct?

2) Seeing how unregulated this all is - is this going to screw up the entire natural world, like?

 

[alsoknownas]

Given the proliferation of fantastic acronyms out there (GNU, PGP, etc.), it's particularly disappointing that they couldn't have given CRISPR an actual palindromic one.

 

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alsoknownas

biochemistry is not my area of expertise

From what I read it appears that CRISPR acts as an immune system for bacteria.

If this arcticle is correct, it gives the impression that the function casΦ performs is uncertain... (casΦ, a small version of CRISPR)

Ironically, within the DNA that these huge phages lug around are parts of the CRISPR system that bacteria use to fight viruses. It's likely that once these phages inject their DNA into bacteria, the viral CRISPR system augments the CRISPR system of the host bacteria, probably mostly to target other viruses.


"It is fascinating how these phages have repurposed this system we thought of as bacterial or archaeal to use for their own benefit against their competition, to fuel warfare between these viruses," said UC Berkeley graduate student Basem Al-Shayeb. Al-Shayeb and research associate Rohan Sachdeva are co-first authors of the Nature paper.

Huge bacteria-eating viruses close gap between life and non-life

Bacterial viruses, called bacteriophages, are simple genetic machines, relying on their bacterial hosts to replicate and spread. But scientists have found hundreds of huge phages that carry a slew of bacterial proteins that the phages evidently use to more efficiently manipulate their microbial...

www.sciencedaily.com

 

[alsoknownas]

Interesting. So it sounds more like they hijack the existing CRISPR system within the bacteria. I guess there's a parallel with HIV in that they are targeting an immune response system (if I'm understanding correctly).

I am concerned that we are on the verge of a huge ethical minefield with targeted gene splicing - not just in humans, but in the rest of the natural world too - with very little public awareness or debate.