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  • From the smallest single-celled organism

  • to the largest creatures on earth,

  • every living thing is defined by its genes.

  • The DNA contained in our genes acts like an instruction manual for our cells.

  • Four building blocks called bases are strung together in precise sequences,

  • which tell the cell how to behave

  • and form the basis for our every trait.

  • But with recent advancements in gene editing tools,

  • scientists can change an organism's fundamental features in record time.

  • They can engineer drought-resistant crops

  • and create apples that don't brown.

  • They might even prevent the spread of infectious outbreaks

  • and develop cures for genetic diseases.

  • CRISPR is the fastest, easiest, and cheapest of the gene editing tools

  • responsible for this new wave of science.

  • But where did this medical marvel come from?

  • How does it work?

  • And what can it do?

  • Surprisingly, CRISPR is actually a natural process

  • that's long functioned as a bacterial immune system.

  • Originally found defending single-celled bacteria and archaea

  • against invading viruses,

  • naturally occurring CRISPR uses two main components.

  • The first are short snippets of repetitive DNA sequences

  • calledclustered regularly interspaced short palindromic repeats,”

  • or simply, CRISPRs.

  • The second are Cas,

  • orCRISPR-associatedproteins

  • which chop up DNA like molecular scissors.

  • When a virus invades a bacterium,

  • Cas proteins cut out a segment of the viral DNA

  • to stitch into the bacterium's CRISPR region,

  • capturing a chemical snapshot of the infection.

  • Those viral codes are then copied into short pieces of RNA.

  • This molecule plays many roles in our cells,

  • but in the case of CRISPR,

  • RNA binds to a special protein called Cas9.

  • The resulting complexes act like scouts,

  • latching onto free-floating genetic material

  • and searching for a match to the virus.

  • If the virus invades again, the scout complex recognizes it immediately,

  • and Cas9 swiftly destroys the viral DNA.

  • Lots of bacteria have this type of defense mechanism.

  • But in 2012, scientists figured out how to hijack CRISPR

  • to target not just viral DNA,

  • but any DNA in almost any organism.

  • With the right tools,

  • this viral immune system becomes a precise gene-editing tool,

  • which can alter DNA and change specific genes

  • almost as easily as fixing a typo.

  • Here's how it works in the lab:

  • scientists design a “guideRNA to match the gene they want to edit,

  • and attach it to Cas9.

  • Like the viral RNA in the CRISPR immune system,

  • the guide RNA directs Cas9 to the target gene,

  • and the protein's molecular scissors snip the DNA.

  • This is the key to CRISPR's power:

  • just by injecting Cas9 bound to a short piece of custom guide RNA

  • scientists can edit practically any gene in the genome.

  • Once the DNA is cut,

  • the cell will try to repair it.

  • Typically, proteins called nucleases

  • trim the broken ends and join them back together.

  • But this type of repair process,

  • called nonhomologous end joining,

  • is prone to mistakes

  • and can lead to extra or missing bases.

  • The resulting gene is often unusable and turned off.

  • However, if scientists add a separate sequence of template DNA

  • to their CRISPR cocktail,

  • cellular proteins can perform a different DNA repair process,

  • called homology directed repair.

  • This template DNA is used as a blueprint to guide the rebuilding process,

  • repairing a defective gene

  • or even inserting a completely new one.

  • The ability to fix DNA errors

  • means that CRISPR could potentially create new treatments for diseases

  • linked to specific genetic errors, like cystic fibrosis or sickle cell anemia.

  • And since it's not limited to humans,

  • the applications are almost endless.

  • CRISPR could create plants that yield larger fruit,

  • mosquitoes that can't transmit malaria,

  • or even reprogram drug-resistant cancer cells.

  • It's also a powerful tool for studying the genome,

  • allowing scientists to watch what happens when genes are turned off

  • or changed within an organism.

  • CRISPR isn't perfect yet.

  • It doesn't always make just the intended changes,

  • and since it's difficult to predict the long-term implications of a CRISPR edit,

  • this technology raises big ethical questions.

  • It's up to us to decide the best course forward

  • as CRISPR leaves single-celled organisms behind

  • and heads into labs, farms, hospitals,

  • and organisms around the world.

From the smallest single-celled organism

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CRISPRはどのようにDNAの編集を可能にするか - アンドレア・M・ヘンレ (How CRISPR lets you edit DNA - Andrea M. Henle)

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    IS LIU に公開 2021 年 01 月 14 日
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