running with scissors--7/21/26
Today's selection-- from The Catalyst by Jonah Berger. CRISPR gene-editing technology:
“Imagine a world in which scientists can create heat- and drought- resistant crops that would thrive on our warming planet, or organisms to sequester carbon and reverse the effects of climate change, or quick and safe fixes for devastating genetic diseases. This is the utopian vision of a future transformed by CRISPR–the gene-editing technology recent books have touted as offering ‘the unthinkable power to control evolution,’ the awesome prospect of ‘editing humanity,’ the chance to direct ‘the future of the human race.’ Yet not everyone is so bullish on CRISPR. There are also dystopian visions of how it might change the world, in which irresponsible individuals or governments use it to create packs of attack animals or legions of obedient superhumans. Is it conceivable that someone could genetically engineer an army of Clone Troopers, as in a Star Wars film?
“CRISPR enables us to modify the genes of practically any organism, from mosquitos to corn to human beings. While many people associate CRISPR with gene-engineering technology, its working parts were actually discovered as a natural process in bacteria, which use it to stave off attacks by the viruses known as phage that we've encountered again and again. The war between bacteria and their viruses has presumably been waged for more than a billion years, and whenever either side invents a new attack, the other comes up with a new counterattack. So, in a sense, the CRISPR system–which works against DNA-based viruses–isn't special but is only one among many antiphage protection systems. But it's the first to have been retooled into a genetic-engineering kit, and it derives its unprecedented power from RNA.
“CRISPR's DNA-cutting machinery is made up of two parts. The first is the Cas9 (CRISPR-associated 9) protein. This protein is an enzyme that works a bit like molecular scissors, physically cutting both strands of the DNA double helix. We've all been told by our parents not to run with scissors, and the same danger applies here: if unguided, these DNAcutting scissors could do a lot of random damage. That's where RNA comes in. In a 2012 breakthrough that would win them the 2020 Nobel Prize in Chemistry, my former postdoc Jennifer Doudna, whom we last saw unlocking the secrets of RN A's structure, and her collaborator Emmanuelle Charpentier discovered that by pairing the Cas9 enzyme with a customized ‘guide RNA,’ they could precisely direct CRISPR's scissors to cut any genetic sequence. Within months after Doudna and Charpentier's discovery was announced, several research teams showed that this RNA-guided genome editing worked in living human cells; these included the groups of Feng Zhang at MIT, George Church at Harvard, and Jennifer's own lab at Berkeley. The stage was set to think about using CRISPR to inactivate cancer-causing oncogenes or the genes that encode misfolded proteins in Alzheimer's disease or amyotrophic lateral sclerosis, among a plethora of possible applications.
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| CRISPR-Cas9 |
“How, exactly, does RNA make such things possible? As we've seen time and again, RNA is an ace at base-pairing, doing the kind of molecular matchmaking that gets nucleic acids talking to each other in productive ways. The RNA molecule associated with the Cas9 protein uses this power to base-pair with one of the two strands of DNA and thereby specify with dazzling precision the exact site of genome editing. Before the advent of this technology, methods for editing specific sites within the human genome were expensive, tedious, and so difficult that only a few labs in the world were able to use them. But nowadays, with a bit of training, undergraduate students can assemble a CRISPR kit to erase a bad mutation in a gene o~ knock out a gene altogether in a few weeks. In my lab, CRISPR is mentioned so often that it's become a verb, like ‘google.’ Once we've ‘CRISPRed’ an alteration into a gene, we can see what effect it has on the cells growing in our Petri dishes.
“My lab is hardly alone in embracing CRISPR. While the more radical applications of this technology are rightly being debated, an estimated 7,000 research laboratories worldwide have already used CRISPR, some making impressive new discoveries. Many more breakthroughs are on the way. Researchers routinely use it to produce genetic alterations not just in cells but in living animals, such as fruit flies and mice. Scientists are generally hype-averse, but many in the life sciences describe the advent of this technology a bit like the Second Coming. They commonly call it the ‘CRISPR Revolution."





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