Monday, 5 June 2017

ATE (What is CRISPR and how does it work?)

F asks "What is CRISPR and how does it work?"

CRISPR is not to be confused with KRISPA which, it turns out, is a highly classified, well it would be, project to take alien technologies and adapt them for civilian use. This project clearly raises many questions, the first of which is "is it nonsense or is it nonsense?"

Viruses have plenty of DNA but don't have the cellular mechanisms needed to reproduce them. Their trick is to get to get a host cell to do it for them. This host cell could be one of yours or mine, or even just a one celled organism such as a bacteria. 

It turns out that many bacteria have a trick up their sleeves for dealing with invading viral DNA. Their own DNA contains a list of the bits of viral DNA that they, or their ancestors, have encountered in the past. To keep things nice and tidy these viral DNA sequences are separated by what we might think of as DNA bookmarks. These take the form of short repeated sections of DNA letters (C, G, A or T) that read the same way backwards as forwards (i.e are palindromes like civic, kayak or racecar). So these sequences are Clustered together in a particular bacterial genome, they're Regularly Inter-spaced, they're Short, they're Palindromic and they Repeat. Hence CRISPR.

To make use of this library of viral DNA the bacteria produces a protein known as CAS9. This protein makes an RNA copy of the viral DNA sequence between the CRISPR genes and then wanders off into the cell. Should it happen to encounter a bit of viral DNA with this same sequence it attaches itself to it and disables it by snipping it in two.

When the viral DNA is snipped in two, it will attempt to repair itself but isn't likely to get it absolutely right and most of the time it's disabled and unable to carry out its dastardly deeds.

Having uncovered all this, some scientists wondered if we might be able to use this mechanism not against viral DNA but to precisely disable particular gene sequences inside other living cells. All you'd need to do is make a sample string of DNA letters matching the gene you want to target and attach CRISPR genes to each end so that the Cas9 enzyme recognises it as a gene sequence to copy. Release this combination into a cell and it will find the targeted sequence, snip it in two and disable it.

Since we now have the technology not only to rapidly sequence DNA, but also to manufacture DNA strands of any sequence we choose, this means that we can use CRISPR to selectively disable what might, for example, be a faulty gene.

Which just leaves one final trick. DNA is good at attempting to repair itself when it's been broken. Like many builders it will tend to make use of the materials at hand. Supply it with a good copy of the gene that you've snipped and there's a good chance that the good copy will be inserted in its place and the cell's DNA will have been repaired.

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