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Scientists Used CRISPR to Engineer a New ‘Superbug’ That’s Invincible to All Viruses

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Can we reprogram existing life at will?

To synthetic biologists, the answer is yes. The central code for biology is simple. DNA letters, in groups of three, are translated into amino acids—Lego blocks that make proteins. Proteins build our bodies, regulate our metabolism, and allow us to function as living beings. Designing custom proteins often means you can redesign small aspects of life—for example, getting a bacteria to pump out life-saving drugs like insulin.

All life on Earth follows this rule: a combination of 64 DNA triplet codes, or “codons,” are translated into 20 amino acids.

But wait. The math doesn’t add up. Why wouldn’t 64 dedicated codons make 64 amino acids? The reason is redundancy. Life evolved so that multiple codons often make the same amino acid.

So what if we tap into those redundant “extra” codons of all living beings, and instead insert our own code?

A team at the University of Cambridge recently did just that. In a technological tour de force, they used CRISPR to replace over 18,000 codons with synthetic amino acids that don’t exist anywhere in the natural world. The result is a bacteria that’s virtually resistant to all viral infections—because it lacks the normal protein “door handles” that viruses need to infect the cell.

But that’s just the beginning of engineering life’s superpowers. Until now, scientists have only been able to slip one designer amino acid into a living organism. The new work opens the door to hacking multiple existing codons at once, copyediting at least three synthetic amino acids at the same time. And when it’s 3 out of 20, that’s enough to fundamentally rewrite life as it exists on Earth.

We’ve long thought that “liberating a subset of…codons for reassignment could improve the robustness and versatility of genetic-code expansion technology,” wrote Drs. Delilah Jewel and Abhishek Chatterjee at Boston College, who were not involved in the study. “This work elegantly transforms that dream into a reality.”

Hacking the DNA Code

Our genetic code underlies life, inheritance, and evolution. But it only works with the help of proteins.

The program for translating genes, written in DNA’s four letters, into the actual building blocks of life relies on a full cellular decryption factory.

Think of DNA’s letters—A, T, C, and G—as a secret code, written on a long slip of crinkled paper wrapped around a spool. Groups of three “letters,” or codons, are the crux—they encode which amino acid a cell makes. A messenger molecule (mRNA), a spy of sorts, stealthily copies the DNA message and sneaks back into the cellular world, shuttling the message to the cell’s protein factory—a sort of central intelligence organization.

There, the factory recruits multiple “translators” to decipher the genetic code into amino acids, aptly named tRNAs. The letters are grouped in threes, and each translator tRNA physically drags its associated amino acid to the protein factory, one by one, so that the factory eventually makes a chain that wraps into a 3D protein.

But like any robust code, nature has programmed redundancy into its DNA-to-protein translation process. For example, the DNA codes TCG, TCA, AGC, and AGT all encode for a single amino acid, serine. While it works in biology, the authors wondered: what if we tap into that code, hijack it, and redirect some of life’s directions using synthetic amino acids?

Hijacking the Natural Code

The new study sees nature’s redundancy as a way to introduce new capabilities into cells.

For us, one question was “could you reduce the number of codons that are used to encode a particular amino acid, and thereby create codons that are free to create other monomers [amino acids]?” asked lead author Dr. Jason Chin.

For example, if TCG is for serine, why not free up the others—TCA, AGC, and AGT— for something else?

It’s a great idea in theory, but a truly daunting task in practice. It means that the team has to go into a cell and replace every single codon they want to reprogram. A few years back, the same group showed that it’s possible in E. Coli, the lab and pharmaceutical’s favorite bug. At that time, the team made an astronomical leap in synthetic biology by synthesizing the entire E. Coli genome from scratch. During the process, they also played around with the natural genome, simplifying it by replacing some amino acid codons with their synonyms—say, removing TCGs and replacing them with AGCs. Even with the modifications, the bacteria were able to thrive and reproduce easily.

It’s like taking a very long book and figuring out which words to replace with synonyms without changing the meaning of sentences—so that the edits don’t physically hurt the bacteria’s survival. One trick, for example, was to delete a protein dubbed “release factor 1,” which makes it easier to reprogram the UAG codon with a brand new amino acid. Previous work showed that this can assign new building blocks to natural codons that are truly “blank”—that is, they don’t encode anything naturally anyways.

A Synthetic Creature

Chin’s team took this much further. Using a method called REXER (replicon excision for enhanced genome engineering through programmed recombination)—yeah, scientists are all about the backcronyms—the team used CRISPR to precisely snip out large parts of the E. Coli bacterial genome, made entirely from scratch inside a test tube.

They then used CRISPR-Cas9, the wunderkind gene editing tool, to snip out and replace more than 18,000 occurrences of extra codons that encode for serine with synonym codons. Because the trick only targeted redundant protein code, the cells were able to go about their normal business—including making serine—but now with multiple natural codons free. It’s like replacing “hi” with “oy,” making “hi” now free to be assigned a completely different meaning.

The team next did some house cleaning. They removed the cells’ natural translators—the tRNAs—that normally read the now-defunct codons without harming the cells. They introduced new synthetic versions of tRNAs to read the new codons. The engineered bacteria were then naturally evolved inside a test tube to grow more rapidly.

The results were spectacular. The superpowered strain, Syn61.Δ3(ev5), is basically a bacterial X-Men that grows rapidly and is resistant to a cocktail of different viruses that normally infects bacteria.

“Because all of biology uses the same genetic code, the same 64 codons and the same 20 amino acids, that means viruses also use the same code…they use the cell’s machinery to build the viral proteins to reproduce the virus,” explained Chin. Now that the bacteria cell can no longer read nature’s standard genetic code, the virus can no longer tap into the bacterial machinery to reproduce—meaning the engineered cells are now resistant to being hijacked by almost any viral invader.

“These bacteria may be turned into renewable and programmable factories that produce a wide range of new molecules with novel properties, which could have benefits for biotechnology and medicine, including making new drugs, such as new antibiotics,” said Chin.

Viral infection aside, the study rewrites what’s possible for synthetic biology.

“This will enable countless applications,” said Jewel and Chatterjee, such as completely artificial biopolymers, that is, materials compatible with biology that could change entire disciplines such as medicine or brain-machine interfaces. Here, the team was able to string up a chain of artificial amino acid building blocks to make a type of molecule that forms the basis of some drugs, such as those for cancer or antibiotics.

But perhaps the most exciting prospect is the ability to dramatically rewrite existing life. Similar to bacteria, we—and all life in the biosphere—operate on the same biological code. The study now shows it’s possible to get past the hurdle of only 20 amino acids making up the building blocks of life by tapping into our natural biological processes.

Next up, the team is looking to potentially further reprogram our natural biological code to encode even more synthetic protein building blocks into bacterial cells. They’ll also move towards other cells—mammalian, for example, to see if it’s possible to compress our genetic code.

Image Credit: nadya_il from Pixabay

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Source: https://singularityhub.com/2021/06/08/scientists-used-crispr-to-engineer-a-new-superbug-thats-invincible-to-all-viruses/

Artificial Intelligence

Scale AI CEO Alex Wang weighs in on software bugs and what will make AV tech good enough

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Scale co-founder and CEO Alex Wang joined us at TechCrunch Sessions: Mobility 2021 this week to discuss his company’s role in the autonomous driving industry and how it’s changed in the five years since its founding. Scale helps large and small AV players establish reliable “ground truth” through data annotation and management, and along the way, the standards for what that means have shifted as the industry matures.

Good data is the “good bones” of autonomous driving systems

Even if two algorithms in autonomous driving might be created more or less equal, their real-world performance could vary dramatically based on what they’re consuming in terms of input data. That’s where Scale’s value prop to the industry starts, and Wang explains why:

If you think about a traditional software system, the thing that will separate a good software system from a bad software system is the code, the quality of the code. For an AI system, which all of these self-driving vehicles or autonomous vehicles are, it’s the data that really separates an amazing algorithm from a bad algorithm. And so one thing we saw was that being one of the stewards and shepherds of high-quality data was going to be incredibly important for the industry, and that’s what’s played out. We work with many of the great companies in the space, from Aurora to Nuro to Toyota to General Motors, and our work with all of them is ensuring that they have really a solid data foundation, so they can build the rest of their stacks on top of it. (Time stamp: 06:24)

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Source: https://techcrunch.com/2021/06/15/scale-ai-ceo-alex-wang-weighs-in-on-software-bugs-and-what-will-make-av-tech-good-enough/

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Artificial Intelligence

Scale AI CEO Alex Wang weighs in on software bugs and what will make AV tech good enough

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Scale co-founder and CEO Alex Wang joined us at TechCrunch Sessions: Mobility 2021 this week to discuss his company’s role in the autonomous driving industry and how it’s changed in the five years since its founding. Scale helps large and small AV players establish reliable “ground truth” through data annotation and management, and along the way, the standards for what that means have shifted as the industry matures.

Good data is the “good bones” of autonomous driving systems

Even if two algorithms in autonomous driving might be created more or less equal, their real-world performance could vary dramatically based on what they’re consuming in terms of input data. That’s where Scale’s value prop to the industry starts, and Wang explains why:

If you think about a traditional software system, the thing that will separate a good software system from a bad software system is the code, the quality of the code. For an AI system, which all of these self-driving vehicles or autonomous vehicles are, it’s the data that really separates an amazing algorithm from a bad algorithm. And so one thing we saw was that being one of the stewards and shepherds of high-quality data was going to be incredibly important for the industry, and that’s what’s played out. We work with many of the great companies in the space, from Aurora to Nuro to Toyota to General Motors, and our work with all of them is ensuring that they have really a solid data foundation, so they can build the rest of their stacks on top of it. (Time stamp: 06:24)

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Source: https://techcrunch.com/2021/06/15/scale-ai-ceo-alex-wang-weighs-in-on-software-bugs-and-what-will-make-av-tech-good-enough/

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Artificial Intelligence

Scale AI CEO Alex Wang weighs in on software bugs and what will make AV tech good enough

Published

on

Scale co-founder and CEO Alex Wang joined us at TechCrunch Sessions: Mobility 2021 this week to discuss his company’s role in the autonomous driving industry and how it’s changed in the five years since its founding. Scale helps large and small AV players establish reliable “ground truth” through data annotation and management, and along the way, the standards for what that means have shifted as the industry matures.

Good data is the “good bones” of autonomous driving systems

Even if two algorithms in autonomous driving might be created more or less equal, their real-world performance could vary dramatically based on what they’re consuming in terms of input data. That’s where Scale’s value prop to the industry starts, and Wang explains why:

If you think about a traditional software system, the thing that will separate a good software system from a bad software system is the code, the quality of the code. For an AI system, which all of these self-driving vehicles or autonomous vehicles are, it’s the data that really separates an amazing algorithm from a bad algorithm. And so one thing we saw was that being one of the stewards and shepherds of high-quality data was going to be incredibly important for the industry, and that’s what’s played out. We work with many of the great companies in the space, from Aurora to Nuro to Toyota to General Motors, and our work with all of them is ensuring that they have really a solid data foundation, so they can build the rest of their stacks on top of it. (Time stamp: 06:24)

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Source: https://techcrunch.com/2021/06/15/scale-ai-ceo-alex-wang-weighs-in-on-software-bugs-and-what-will-make-av-tech-good-enough/

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Artificial Intelligence

Extra Crunch roundup: TC Mobility recaps, Nubank EC-1, farewell to browser cookies

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What, exactly, are investors looking for?

Early-stage founders, usually first-timers, often tie themselves in knots as they try to project the qualities they hope investors are seeking. In reality, few entrepreneurs have the acting skills required to convince someone that they’re patient, dedicated or hard-working.

Johan Brenner, general partner at Creandum, was an early backer of Klarna, Spotify and several other European startups. Over the last two decades, he’s identified five key traits shared by people who create billion-dollar companies.


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“A true unicorn founder doesn’t need to have all of those capabilities on Day One,” says Brenner, “but they should already be thinking big while executing small and demonstrating that they understand how to scale a company.”

Drawing from observations gleaned from working with founders like Spotify’s Daniel Ek, Sebastian Siemiatkowski from Klarna, and iZettle’s Jacob de Geer and Magnus Nilsson, Brenner explains where “VC FOMO” comes from and how it drives dealmaking.

We’re running a series of posts that recap conversations from last week’s virtual TC Mobility conference, including an interview with Refraction AI’s Matthew Johnson, a look at how autonomous delivery startups are navigating the regulatory and competitive landscape, and much more. There are many more recaps to come; click here to find them all.

Thanks very much for reading Extra Crunch!

Walter Thompson
Senior Editor, TechCrunch
@yourprotagonist

How contrarian hires and a pitch deck started Nubank’s $30 billion fintech empire

Image Credits: Nigel Sussman

Founded in 2013 and based in São Paulo, Brazil, Nubank serves more than 34 million customers, making it Latin America’s largest neobank.

Reporter Marcella McCarthy spoke to CEO David Velez to learn about his efforts to connect with consumers and overcome entrenched opposition from established players who were friendly with regulators.

In the first of a series of stories for Nubank’s EC-1, she interviewed Velez about his early fundraising efforts. For a balanced perspective, she also spoke to early Nubank investors at Sequoia and Kaszek Ventures, Latin America’s largest venture fund, to find out why they funded the startup while it was still pre-product.

“There are people you come across in life that within the first hour of meeting with them, you know you want to work with them,” said Doug Leone, a global managing partner at Sequoia who’d recruited Velez after he graduated from grad school at Stanford.

Marcella also interviewed members of Nubank’s founding team to better understand why they decided to take a chance on a startup that faced such long odds of success.

“I left banking to make a fifth of my salary, and back then, about $5,000 in equity,” said Vitor Olivier, Nubank’s VP of operations and platforms.

“Financially, it didn’t really make sense, so I really had to believe that it was really going to work, and that it would be big.”

Despite flat growth, ride-hailing colossus Didi’s US IPO could reach $70B

Image Credits: Didi

In his last dispatch before a week’s vacation, Alex Wilhelm waded through the numbers in Didi’s SEC filing. The big takeaways?

“While Didi managed an impressive GTV recovery in China, its aggregate numbers are flatter, and recent quarterly trends are not incredibly attractive,” he writes.

However, “Didi is not as unprofitable as we might have anticipated. That’s a nice surprise. But the company’s regular business has never made money, and it’s losing more lately than historically, which is also pretty rough.”

What’s driving the rise of robotaxis in China with AutoX, Momenta and WeRide

AutoX, Momenta and WeRide took the stage at TC Sessions: Mobility 2021 to discuss the state of robotaxi startups in China and their relationships with local governments in the country.

They also talked about overseas expansion — a common trajectory for China’s top autonomous vehicle startups — and shed light on the challenges and opportunities for foreign AV companies eyeing the massive Chinese market.

The air taxi market prepares to take flight

Image Credits: Bryce Durbin

“As in any disruptive industry, the forecast may be cloudier than the rosy picture painted by passionate founders and investors,” Aria Alamalhodaei writes. “A quick peek at comments and posts on LinkedIn reveals squabbles among industry insiders and analysts about when this emerging technology will truly take off and which companies will come out ahead.”

But while some electric vertical take-off and landing (eVTOL) companies have no revenue yet to speak of — and may not for the foreseeable future — valuations are skyrocketing.

“Electric air mobility is gaining elevation,” she writes. “But there’s going to be some turbulence ahead.”

The demise of browser cookies could create a Golden Age of digital marketing

Though some may say the doomsday clock is ticking toward catastrophe for digital marketing, Apple’s iOS 14.5 update, which does away with automatic opt-ins for data collection, and Google’s plan to phase out third-party cookies do not signal a death knell for digital advertisers.

“With a few changes to short-term strategy — and a longer-term plan that takes into account the fact that people are awakening to the value of their online data — advertisers can form a new type of relationship with consumers,” Permission.io CTO Hunter Jensen writes in a guest column. “It can be built upon trust and open exchange of value.”

If offered the right incentives, Jensen predicts, “consumers will happily consent to data collection because advertisers will be offering them something they value in return.”

How autonomous delivery startups are navigating policy, partnerships and post-pandemic operations

Nuro second gen R2 delivery vehicle

Image Credits: Nuro

We kicked off this year’s TC Sessions: Mobility with a talk featuring three leading players in the field of autonomous delivery. Gatik co-founder and chief engineer Apeksha Kumavat, Nuro head of operations Amy Jones Satrom, and Starship Technologies co-founder and CTO Ahti Heinla joined us to discuss their companies’ unique approaches to the category.

The trio discussed government regulation on autonomous driving, partnerships with big corporations like Walmart and Domino’s, and the ongoing impact the pandemic has had on interest in the space.

Waabi’s Raquel Urtasun explains why it was the right time to launch an AV technology startup

Image Credits: Waabi via Natalia Dola

Raquel Urtasun, the former chief scientist at Uber ATG, is the founder and CEO of Waabi, an autonomous vehicle startup that came out of stealth mode last week. The Toronto-based company, which will focus on trucking, raised an impressive $83.5 million in a Series A round led by Khosla Ventures.

Urtasun joined Mobility 2021 to talk about her new venture, the challenges facing the self-driving vehicle industry and how her approach to AI can be used to advance the commercialization of AVs.

Coinsmart. Beste Bitcoin-Börse in Europa
Source: https://techcrunch.com/2021/06/15/extra-crunch-roundup-tc-mobility-recaps-nubank-ec-1-farewell-to-browser-cookies/

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