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Biological Chemistry

Video: How CRISPR-Cas9 works

The Nobel-winning gene-editing technique enables scientists to precisely alter an organism’s DNA

by Kerri Jansen
October 9, 2020

Credit: Darren Weaver/Andrew Sobey/ACS Productions/C&EN

CRISPR-Cas9 combines a protein that can neatly snip DNA with a molecule that guides those molecular shears to a specific spot in an organism’s genome. Watch this video to learn how it works.

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The following is the script for the video.

Kerri Jansen: The gene-editing method known as CRISPR-Cas9 has transformed the molecular life sciences. The Nobel Prize–winning method developed by Emmanuelle Charpentier and Jennifer A. Doudna enables scientists to precisely alter an organism’s DNA, promising improved crops, new treatments for disease, and more. Here’s how it works.

CRISPR-Cas9 combines a protein that can neatly snip DNA with a molecule that guides those molecular shears to a specific spot in an organism’s genome. CRISPR’s creators adapted the tool from a naturally occurring bacterial defense system.

When bacteria survive a viral attack, they incorporate snippets of the virus’s DNA into their own genomes. Those stolen segments—and the genetic padding between them—are called clustered regularly interspaced short palindromic repeats, or CRISPR. If the virus attacks again, the bacteria use those CRISPR segments as a template to create strands of RNA that home in on the corresponding sequence in the virus’s genome. The CRISPR RNA carries along a protein called Cas9 to the target location on the DNA. The protein disarms the virus by cutting its DNA at that spot.

Charpentier and Doudna were amazed by this clever bacterial immune system and wondered if they could reprogram it to make precise cuts, or edits, to any DNA. The two scientists created a new molecule called guide RNA, which can be easily customized to mirror any DNA strand.

That custom guide RNA molecule is like a homing beacon. It steers Cas9, the molecular scissors, to cut a precise portion of DNA.

With CRISPR-Cas9, researchers can now see what happens when they turn a gene off by cutting it. Or they can program the CRISPR-Cas9 complex to insert a new DNA sequence to repair or edit a gene.

The technique has become widespread in labs since Charpentier and Doudna first described it in 2012. Scientists have now used CRISPR to edit the DNA of organisms across the tree of life—butterflies, mushrooms, coffee, cuttlefish, and, yes, even humans. And while it may still be several years before some of the more ambitious applications are proven to work—such as using CRISPR to cure genetic diseases—CRISPR has proven indisputably useful as a research tool. Scientists around the world have published thousands of experiments using the gene-editing tool in their research, and the technology has spawned dozens of companies. CRISPR likely has many more surprises in store for us, and it all started by studying that curious little bacterial immune system.

Correction:

This video was updated on Oct. 14, 2020, to correct video footage of cuttlefish. The original clip showed a species of squid.

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