Next-Gen CRISPR – pasting whole genes without cutting

PASTE is a three-part CRISPR tool invented at the MIT McGovern Institute for Brain Research. It’s composed of a modified CRISPR-Cas9 (it’s called nickase because it nicks a single DNA strand instead of cutting both) and two effectors: RT stands for reverse transcriptase (just like in prime editing) while LSR means large serine recombinase.

This brand-new molecular machine writes the genome in three steps. Step 1: the nickase finds the desired site. Step 2: the reverse transcriptase inserts a landing pad. Step 3: the recombinase lands there and delivers its large DNA cargo. The aim is to replace whole genes, when fixing mutations is not enough (one example is cystic fibrosis). Here are the links to learn more:

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The race of Liu’s CRISPR machines

From the base-editing idea first sketched out via email in 2013, to the invention of prime-editing in 2019. From the progeria mutation fixed in mice in 2021 to the upcoming clinical trial for coronary heart disease. The updated story of the most advanced CRISPR tools told by Harvard’s David Liu is not to be missed (here’s the link to the Life Itself conference organized by CNN).

RNA moments

Soon after co-discovering the double helix, Francis Crick coined the term “central dogma of biology” to illustrate the flow of genetic information within biological systems. The basic idea is simple: DNA is the king of the cell, proteins are its major workforce, and RNA is a sort of a middle manager. He later admitted that dogma was a poor word choice for a rule that has exceptions. Indeed, he became one of the proponents of the RNA world hypothesis, where RNA is the primordial substance in the evolutionary history of life on Earth. We can only guess what the great British scientist might say about RNA taking the stage today.

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Prime-edited rice & CRISPR golden rice

Do you remember prime editing? It’s the new ‘search-and-replace’ genome editing technology that mediates targeted insertions, deletions, all 12 possible base-to-base conversions, and combinations thereof. The first good news is that David Liu et al. adapted prime editors for use in rice and wheat, so don’t miss their paper in Nature Biotechnology.

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Crazy 4 Prime Editing

Great piece of science by the Liu Lab in Nature, describing the brand new “Search-and-replace genome editing without double-strand breaks or donor DNA”. How is the CRISPR community reacting?

Best quote: “One of those ‘Yay, science!!!’ kind of moments” (Fyodor Urnov quoted in Science)

Most ironic: “Congratulations @davidrliu. We’d probably have published this paper as well (The CRISPR Journal tweet)

Best title: Genome Editing Heads to Primetime (Genetic Engineering and Biotechnology News)

Most understated: A New Gene Editing Tool Could Make CRISPR More Precise (Smithsonian Mag)

Most hyped: A New CRISPR Technique Could Fix Almost All Genetic Diseases (Wired)