RNA-targeting enzyme expands the CRISPR toolkit

Exploring diversity among bacterial immune systems, McGovern Institute scientists uncovere a programmable system for precisely targeting and modifying RNA.

Brain and cognitive sciences, McGovern Institute, CRISPR, DNA, RNA, Genome editing, Genetic engineering, Research, School of Science, Omar Abudayyeh, Jonathan Gootenberg, reported

McGovern Fellows Jonathan Gootenberg (left) and Omar Abudayyeh in their lab Photo: Caitlin Cunningham

Brain and cognitive sciences, McGovern Institute, CRISPR, DNA, RNA, Genome editing, Genetic engineering, Research, School of Science, Omar Abudayyeh, Jonathan Gootenberg, reported

DNA tools in the CRISPR toolkit (red) are approaching capacity, but researchers are now beginning to find new tools to edit RNA (blue). Illustration: Steve Dixon

Researchers at MIT’s McGovern Institute for Brain Research have discovered a bacterial enzyme that they say could expand scientists’ CRISPR toolkit, making it easy to cut and edit RNA with the kind of precision that, until now, has only been available for DNA editing. The enzyme, called Cas7-11, modifies RNA targets without harming cells, suggesting that in addition to being a valuable research tool, it provides a fertile platform for therapeutic applications.

“This new enzyme is like the Cas9 of RNA,” says McGovern Fellow Omar Abudayyeh, referring to the DNA-cutting CRISPR enzyme that has revolutionized modern biology by making DNA editing fast, inexpensive, and exact. “It creates two precise cuts and doesn’t destroy the cell in the process, like other enzymes,” he adds.

Up until now, only one other family of RNA-targeting enzymes, Cas13, has extensively been developed for RNA targeting applications. However, when Cas13 recognizes its target, it shreds any RNAs in the cell, destroying the cell along the way. Like Cas9, Cas7-11 is part of a programmable system; it can be directed at specific RNA targets using a CRISPR guide. Abudayyeh, McGovern Fellow Jonathan Gootenberg, and their colleagues discovered Cas7-11 through a deep exploration of the CRISPR systems found in the microbial world. Their findings were recently reported in the journal Nature.

Exploring natural diversity

Like other CRISPR proteins, Cas7-11 is used by bacteria as a defense mechanism against viruses. After encountering a new virus, bacteria that employ the CRISPR system keep a record of the infection in the form of a small snippet of the pathogen’s genetic material. Should that virus reappear, the CRISPR system is activated, guided by a small piece of RNA to destroy the viral genome and eliminate the infection.

These ancient immune systems are widespread and diverse, with different bacteria deploying different proteins to counter their viral invaders.

“Some target DNA, some target RNA. Some are very efficient in cleaving the target but have some toxicity, and others do not. They introduce different types of cuts, they can differ in specificity — and so on,” says Eugene Koonin, an evolutionary biologist at the National Center for Biotechnology Information.

Abudayyeh, Gootenberg, and Koonin have been scouring genome sequences to learn about the natural diversity of CRISPR systems — and to mine them for potential tools. The idea, Abudayyeh says, is to take advantage of the work that evolution has already done in engineering protein machines.

“We don’t know what we’ll find,” Abudayyeh says, “but let’s just explore and see what’s out there.”

As the team was poring through public databases to examine the components of different bacterial defense systems, a protein from a bacterium that had been isolated from Tokyo Bay caught their attention. Its amino acid sequence indicated that it belonged to a class of CRISPR systems that use large, multiprotein machines to find and cleave their targets. But this protein appeared to have everything it needed to carry out the job on its own. Other known single-protein Cas enzymes, including the Cas9 protein that has been widely adopted for DNA editing, belong to a separate class of CRISPR systems — but Cas7-11 blurs the boundaries of the CRISPR classification system, Koonin says.

The enzyme, which the team eventually named Cas7-11, was attractive from an engineering perspective, because single proteins are easier to deliver to cells and make better tools than their complex counterparts. But its composition also signaled an unexpected evolutionary history. The team found evidence that through evolution, the components of a more complex Cas machine had fused together to make the Cas7-11 protein. Gootenberg equates this to discovering a bat when you had previously assumed that birds are the only animals that fly, thereby recognizing that there are multiple evolutionary paths to flight. “It totally changes the landscape of how these systems are thought about, both functionally and evolutionarily,” he says.

Precision editing

When Gootenberg and Abudayyeh produced the Cas7-11 protein in their lab and began experimenting with it, they realized this unusual enzyme offered a powerful means to manipulate and study RNA. When they introduced it into cells along with an RNA guide, it made remarkably precise cuts, snipping its targets while leaving other RNA undisturbed. This meant they could use Cas7-11 to change specific letters in the RNA code, correcting errors introduced by genetic mutations. They were also able to program Cas7-11 to either stabilize or destroy particular RNA molecules inside cells, which gave them the ability to adjust the levels of the proteins encoded by those RNAs.

Abudayyeh and Gootenberg also found that Cas7-11’s ability to cut RNA could be dampened by a protein that appeared likely to also be involved in triggering programmed cell death, suggesting a possible link between CRISPR defense and a more extreme response to infection.

The team showed that a gene therapy vector can deliver the complete Cas7-11 editing system to cells and that Cas7-11 does not compromise cells’ health. They hope that with further development, the enzyme might one day be used to edit disease-causing sequences out of a patient’s RNA so their cells can produce healthy proteins, or to dial down the level of a protein that is doing harm due to genetic disease.

“We think that the unique way that Cas7-11 cuts enables many interesting and diverse applications,” Gootenberg says, noting that no other CRISPR tool cuts RNA so precisely. “It’s yet another great example of how these basic-biology driven explorations can yield new tools for therapeutics and diagnostics,” he adds. “And we’re certainly still just scratching the surface of what’s out there in natural diversity.”

Internet Explorer Channel Network
News Related

OTHER NEWS

Microplastics are found in the blood of farm animals including cows and pigs for the first time - raising concerns about their movement through the food chain

Microplastics have been found in the blood of cows and pigs for the first timeIt has sparked concern about their movement through the food chain to humansScientists believe discovery could have serious implications for public healthPlastic particles entering bloodstreams risk being deposited in people's organs Read more »

Strictly star Anton du Beke opens up about secret wedding

Anton Du Beke is wowing in his new role as a full-time judge on Strictly Come Dancing – and has revealed that he sprung the idea of marriage on his ... Read more »

Kitten Tiny Tim ‘doing amazingly' after being found alone in garden at week old

A kitten nicknamed Tiny Tim is “doing amazingly” after being found in a garden away from his mother. The cat is believed to have been around a week old when ... Read more »

Kiss frontman Gene Simmons lists Las Vegas Valley mansion for sale for £10 million five months after buying it

(ES Composite) Less than five months after buying his striking Las Vegas Valley mansion, Kiss frontman Gene Simmons has listed it for sale – for £2.9 million more than he ... Read more »

Rachel Riley says she was groped by 'Countdown' fan

Rachel Riley stars as the maths guru on ‘Countdown‘. (Channel 4) Rachel Riley has told how she was once groped by a Countdown fan in front of his wife, before ... Read more »

Parents who are occasionally abrupt with their children may be guilty of 'mild neglect', says NSPCC

Mother scolding son in living room – takasuu Parents who are occasionally abrupt with their children and hold low-key celebrations may be guilty of ‘mild neglect’, according to NSPCC guidance. ... Read more »

Boris Johnson: Nothing to suggest lockdown is on the cards

Boris Johnson has said that despite a rise in the number of Covid-19 cases, a winter lockdown is unlikely at the moment. Read more »

'Strictly's' AJ and Kai rival Adam and Katya's 'almost kiss'

AJ Odudu and Kai Widdrington appeared to come close to kissing. (BBC) AJ Odudu and Kai Widdrington have become the latest Strictly couple to “almost kiss” at the end of ... Read more »

BharatPe claims PhonePe ‘turned turtle' in court on its stand against usage of ‘Pe'

The PhonePe app (Representative image: Twitter/@PhonePe_) The courtroom clash between digital payment players PhonePe and BharatPe has now turned into a war of words with BharatPe calling PhonePe’s statement on ... Read more »

Ruth Langsford reacts to Strictly's Rylan Clark-Neal's surprise body transformation – see photo

Strictly: It Takes Two star Rylan Clark-Neal recently revealed a look at his body transformation on Instagram, and Ruth Langsford is apparently just as impressed as he fans were. SEE: ... Read more »

Halloween's bone-chilling villain Michael Myers is ‘homophobic' in new film

A gruesome murder of a gay couple in Halloween Kills has resulted in some horror fans calling the villain Michael Myers “homophobic”. The long running Halloween franchise has largely focused ... Read more »

Climate map shows three million homes that could be flooded by 2050

Map shows areas in Portsmouth and Great Yarmouth in danger of flooding by 2050. (Gamma) A new climate change flood map has predicted three million homes could become unsellable if ... Read more »

Ant and Dec star in new promo for 'I'm A Celebrity' 2021

Ant & Dec star in a brand-new trailer for the upcoming series of I’m A Celebrity…Get Me Out Of Here! This year’s series returns to stunning Gwrych Castle in North ... Read more »

Roomba j7+ review: I tried iRobot's newest robotic vacuum and here's what I thought

Looking for more of the best deals, sales and product recommendations? Sign up for Yahoo Lifestyle Canada’s newsletter! The latest Roomba innovation has just arrived, and I put it to ... Read more »

Armourer, 24, on Alec Baldwin film 'wasn't sure' if she was ready for movie set roles

Hannah Gutierrez told a podcast that she had a ‘natural knack’ for working with guns – VoicesoftheWest The 24-year-old head armourer on the set where Alec Baldwin fatally shot a ... Read more »

COVID-19: Holidaymakers could be asked to have third jab to travel as 'vaccine passport concept will evolve', care minister says

British holidaymakers may in the future be asked to have a third COVID-19 vaccine dose before they are able to easily travel and return from abroad, a minister told Sky ... Read more »

New infant planet discovered by researchers in Hawaii

An international research team led by the University of Hawaiʻi at Mānoa has discovered one of the youngest planets ever observed. The findings, published in Monthly Notices of the Royal ... Read more »

Zebra foal makes public debut at Mexico zoo

The foal represents a growing hope for the conservation of the Grevy’s zebra (Equus grevyi), also known as the imperial zebra, which is the most threatened of the three species ... Read more »

Elephants have evolved to be tuskless in response to ivory poaching, study finds

Researchers in Mozambique found a dramatic shift within 15 years, illustrating how human activity can accelerate genetic changes in other species. Read more »

Kate Middleton's diet and workout routine is surprisingly normal

Photo credit: Max Mumby/Indigo – Getty Images As a mother of three and one of the most recognised (and judging by her diary, busiest) women in the world, it must ... Read more »

NASA's uncrewed Artemis moon mission is due to launch in February, following delays caused by the pandemic and Hurricane Ida

An artist’s illustration depicts Artemis astronauts on the moon. NASA via AP NASA announced its Artemis 1 uncrewed mission to the moon is aiming for liftoff in February 2022. The ... Read more »

Elton John calls out ‘f***ing big mouth' Ed Sheeran after singer ruins ‘secret' Christmas song news

Elton John calls out ‘f***ing big mouth’ Ed Sheeran after singer ruins ‘secret’ Christmas song news Elton John has called Ed Sheeran a “f***ing big mouth” after the singer prematurely ... Read more »

Three years after the EU demanded single-use plastic ban by 2021... has it worked?

Single-use plastic often finds its way into the ocean (Getty) This article is part of Yahoo's 'On This Day' series ‘By 2050, there will be more plastic than fish in ... Read more »

'Dune': The many failed attempts to adapt Frank Herbert's 'unfilmable' sci-fi classic

The title treatment for Denis Villeneuve‘s adaptation of Frank Herbert‘s Dune. (Warner Bros.) You’ll find some people who think the 1984 David Lynch adaptation of Frank Herbert’s epic sci-fi book ... Read more »

'Strictly' fans think Adam Peaty's tight jeans were to thank for highest Samba score of series

Adam Peaty danced the Samba. (BBC) Adam Peaty has earned the highest Samba score of Strictly Come Dancing 2021 – but viewers suspect the judges were distracted from his moves ... Read more »

‘Predator' jailed for spiking woman's drink before recording sex assault at hotel

Sean Howarth, 31, was sentenced to seven years and two months in prison. (PA) A ‘predator’ has been jailed after he spiked a woman’s drink with cocaine, sexually assaulted her ... Read more »

Greta Thunberg: 'We need public pressure, not just summits'

Climate activist Greta Thunberg has told the BBC that summits will not lead to action on climate goals unless the public demand change too. In a wide-ranging interview ahead of ... Read more »

10 nutritionist-approved foods that can help you feel less stressed

Certain foods can help relieve stress. (Getty Images) Stress is a somewhat inevitable part of life. At one point or another everyone will feel stressed-out, whether it’s due to work, ... Read more »

London's Natural History Museum ice rink returns

Ice skating returns to London‘s Natural History Museum but it’s for the last time The annual winter tradition will come to an end after 16 years to make space for ... Read more »

Richard Gere summoned to testify at Italy's leader trial

Hollywood star Richard Gere has been summoned to testify as Italy’s former interior minister and far-right leader Matteo Salvini went on trial Saturday for allegedly illegally blocking over 100 migrants ... Read more »

Judge rules for Tennessee school district's mask mandate

© Provided by Associated Press FILE – In this Friday, Aug. 20, 2021, file photo, kindergarten teacher Amber Updegrove interacts with her students at Warner Arts Magnet Elementary in Nashville, ... Read more »

It's Offish: Carla Abellana And Tom Rodriguez Are Now Married

© Provided by Cosmopolitan Philippines It looks like Carla Abellana and Tom Rodriguez‘s wedding took place earlier than expected! It was first reported that the couple is set to wed ... Read more »

Lawmaker tests positive for COVID hours after voting on House floor

Representative Glenn “GT” Thompson, who is vaccinated, has tested positive for COVID-19, his office confirmed Friday. The Pennsylvania Republican had voted on the House floor earlier Friday, according to House records. © ... Read more »

Forget Keita: Klopp must unleash £120k-p/w LFC outcast on Sunday, he impressed v Atleti -opinion

© Provided by Football FanCast Premier League – Watford v Liverpool Liverpool face another tough task at the weekend with a trip to Old Trafford to take on Manchester United ... Read more »

Ben Simmons trade rumors: 'People should buckle in,' says 76ers president Daryl Morey

It’s safe to say that the 76ers are in no rush to trade Ben Simmons. Ahead of Philadelphia’s home opener against Brooklyn on Friday, 76ers president of basketball operations Daryl ... Read more »

Baby octopuses grow hundreds of temporary organs, then lose them without a trace

Your internal organs grow and change throughout your life, but rarely do they vanish without a trace. For baby octopuses, things are not so simple. © Provided by Live Science ... Read more »

Micro Center leaks specs and pricing for Intel's new Alder Lake Core i9 CPU

© Illustration by Alex Castro / The Verge Even though someone managed to secure early purchases of a couple of Core i9-12900K CPUs, we still didn’t have detailed information about ... Read more »

Amanda Holden jets off on another glamorous holiday amid Covid-19 pandemic

The star soaks up the sun on another holiday to a mystery destination (AmandaHolden/Instagram) Amanda Holden soaked up the sun on yet another holiday amid the ongoing Covid pandemic. Already ... Read more »

Alec Baldwin fatally shoots woman with prop gun on set of new movie Rust - victim named as Halyna Hutchins

A woman has died and a man has been injured after actor Alec Baldwin discharged a prop firearm on the set of new Western movie Rust. Read more »

COVID-19: Online groups attempt to confront MPs over their 'evil actions'

Anti-vaccination and anti-lockdown protesters are organising themselves online to confront MPs in person, Sky News has found. Read more »
On free-english-test.com you will find lots of free English exam practice materials to help you improve your English skills: grammar, listening, reading, writing, ielts, toeic