Der umfassende Leitfaden zum Genome Editing.
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What is CRISPR?

CRISPR is a bacterial immune system that scientists reprogrammed into a tool for finding and changing a chosen piece of DNA.

Die Kurzantwort

Bacteria get infected by viruses too, and they defend themselves by keeping a genetic scrapbook of past attackers. When a virus returns, the bacterium makes an RNA copy of the relevant scrapbook entry, hands it to a protein that cuts DNA, and the protein hunts down anything matching. Scientists realised you could put any address you liked in that scrapbook — and suddenly you had a programmable tool for finding one specific sequence among three billion letters.

CRISPR — clustered regularly interspaced short palindromic repeats — describes arrays in bacterial and archaeal genomes in which spacers derived from previously encountered phage sit between repeat sequences. Transcribed spacers guide Cas nucleases to complementary sequence. In 2012 Jinek et al. showed that Cas9 could be programmed with a synthetic single guide RNA to cleave chosen DNA; in January 2013 the Zhang and Church laboratories independently demonstrated this in human cells.

What the acronym means

Clustered Regularly Interspaced Short Palindromic Repeats — a description of what the sequence looks like in a bacterial genome, coined by Francisco Mojica in the early 2000s, long before anyone imagined using it as a tool. In practice 'CRISPR' now usually means the editing technology, which is a little like calling a car a 'horseless carriage': the name records where it came from, not what it does.

How it finds one place in three billion letters

  1. A guide RNA about 20 letters long is designed to match the target.
  2. The guide is loaded into a Cas protein; neither works alone.
  3. The complex scans the genome for a short signal called a PAM — without one, it will not cut, which limits where you can aim.
  4. Where the guide matches, the DNA opens and pairs with it.
  5. The protein cuts, and the cell's repair machinery makes the actual change.
Where the analogy breaks downEveryone calls CRISPR 'molecular scissors'. The phrase hides the most important detail: the scissors do not edit anything. They break DNA. The cell repairs the break, and that repair is the edit — which is why the same cut can give different results in different cells, and why breaking a gene is far easier than fixing one.

Why it took over so fast

Zinc fingers and TALENs could already do targeted editing, but retargeting them meant engineering a new protein — months of specialist work. Retargeting CRISPR means ordering a different short RNA. The published method spread through the world's laboratories within a year, and the Nobel Prize in Chemistry followed in 2020.

Common questions

What does CRISPR stand for?

Clustered Regularly Interspaced Short Palindromic Repeats — a description of the repeating pattern found in bacterial genomes.

Who invented CRISPR?

Nobody invented it; bacteria evolved it. Its function was worked out over decades by researchers including Francisco Mojica, Rodolphe Barrangou and Philippe Horvath. Jennifer Doudna and Emmanuelle Charpentier showed in 2012 that it could be programmed to cut chosen DNA, with Virginijus Šikšnys publishing closely related work the same year, and Feng Zhang's and George Church's laboratories demonstrated it in human cells in January 2013.

Is CRISPR being used on people?

Yes. One CRISPR-based medicine is approved for sickle cell disease and beta thalassemia, and dozens of trials are running in other conditions. Approved use is somatic — it changes cells in one person and is not inherited.

Sources

Connected in the Atlas

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Technologies

CRISPR-Cas9