A new method of discovering the genetic sequences that make CRISPR work could expand the use of this gene-editing system.
Most headlines about CRISPR, a bacteria-derived tool that can slice and edit a genome, are about a particular set of genes and proteins called CRISPR-Cas9. CRISPR-Cas9 has shown great promise for targeted gene therapies for conditions such as Duchenne muscular dystrophy (CEP, Feb. 2016, pp. 6–9) and liver disease (CEP, Mar. 2016, pp. 6–8). But CRISPR-Cas9 is just one of many types of CRISPR-Cas systems that work in different ways and can have different effects.
The challenge to unlocking the use of many of these CRISPR systems is to figure out the code that makes them tick. In bacterial immune systems, CRISPR-Cas works by identifying a genetic sequence from a viral invader and copying it between sets of clustered regularly interspaced short palindromic repeats (CRISPR). Guided by this sequence, the Cas protein moves along the invader’s genome, searching for a match. When it finds a match, the Cas protein can bind to, snip, or excise the DNA or RNA, depending on the type of Cas protein.
Researchers have customized this tool for their own uses, programming CRISPR-Cas9 to not only cleave DNA, but to insert new genes as well. This ability relies on one of CRISPR’s lesser-known acronyms, though: PAMs, or protospacer-adjacent motifs. In order to develop the right CRISPR-Cas system, researchers must identify the PAMs corresponding to the DNA or RNA sequence of interest.
PAMs are genetic segments, usually just a few nucleotides long, that sit...
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