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Arrakis Therapeutics Publishes Advanced Research Method To Systematically Identify RNA-Targeted Small Molecules

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Technology platform tool, PEARL-seq™, identifies binding sites in RNA by integrating proprietary bioinformatics workflow with chemical biology techniques for the rational design of rSM therapeutics

Arrakis Therapeutics, a biopharmaceutical company pioneering the discovery of a new class of small molecule medicines that directly target RNA, today announced the publication of data demonstrating the capabilities of its proprietary PEARL-seq™ technology for the systematic identification of binding sites in RNA molecules, as an advanced research method to facilitate the discovery of RNA-targeted small molecule (rSM) medicines. The research was published online in the American Chemical Society’s peer-reviewed journal, ACS Chemical Biology, in an article titled “PEARL-seq: A Photoaffinity Platform for the Analysis of Small Molecule-RNA Interactions.” PEARL-seq, which stands for Photoaffinity Evaluation of RNA Ligation-sequencing, is one of the chemical biology components of Arrakis’ proprietary end-to-end platform for discovery of rSM medicines.

“PEARL-seq represents our innovative approach to establish target engagement, identify binding sites on the RNA, and learn about selectivity across the transcriptome,” said Jennifer C. Petter, Ph.D., Founder and Chief Scientific Officer of Arrakis. “As part of Arrakis’ mission to drug RNA, we are building and refining the tools needed to discover and design rSMs against important RNA targets involved in disease.”

The published study describes the development of PEARL-seq, which utilizes photoaffinity labeling of RNA in combination with next-generation sequencing and a dedicated bioinformatic analysis pipeline. Overall, the published work demonstrates the ability of the PEARL-seq platform to identify ligand binding sites within a model aptamer RNA as well as to identify potential off-target binding interactions. These data, combined with conventional RNA structure probing methods, can be used to generate and refine two- and three-dimensional structures of RNA-small molecule complexes, thereby facilitating the rational design of rSM therapeutics.

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Key findings of the study include:

  • PEARL-seq enabled the identification of ligand binding sites as well as selectivity across RNAs in a single experiment.
  • The research showed that photoaffinity labels could be tethered to rSMs without disrupting the binding interactions between the rSM and the RNA. Upon activation with UV light, the rSM irreversibly crosslinks to the RNA, enabling mapping of the interaction by sequencing analysis.
  • The research further integrated RNA binding site characterization with transcriptome-wide sequencing to assess small molecule selectivity across the transcriptome.
  • Beyond binding site identification for directing RNA-targeted medicines, the results were integrated with multiple chemical probing data streams to support better informed two- and three-dimensional RNA structural predictions.
  • The researchers demonstrated the use of a DNA-encoded library screen to identify a novel small-molecule ligand to an aptamer RNA and used PEARL-seq to confirm a shared binding site with the original ligand.

“In this publication, we demonstrate the power of PEARL-seq to drive the rational design of rSMs,” said Herschel Mukherjee, a chemist at Arrakis and a co-author of the publication. “Consistent with our platform-based approach, we combined photoaffinity labeling of RNA with refined sequencing and bioinformatics pipelines to develop a highly sensitive method for studying small molecule-RNA interactions.”

“It was exciting to be a part of this close collaboration among the biology, chemistry and computational teams at Arrakis, along with external partners,” added Craig Blain, a senior scientist and co-author of the publication. “‘Thriving as a team is an important part of how we work at Arrakis and has helped us build the PEARL-seq platform, a critical part of our mission to drug RNA.”

Arrakis’ Platform for Developing rSM Medicines

Arrakis has developed a proprietary drug discovery platform for the systematic discovery and design of RNA-targeted small molecules (rSMs), by identifying small molecules that bind to and modulate RNA to predictably impact disease-related biology. The comprehensive drug discovery toolkit integrates leading‐edge RNA bioinformatics and chemical biology tools, RNA‐specific chemical and biological assays, and RNA-directed medicinal chemistry. By leveraging the best existing tools with Arrakis’ exclusive technologies, we can, for the first time on an industrial scale, identify small molecules that modulate RNA function and predictably impact important biology in disease processes.

About Arrakis Therapeutics

Arrakis Therapeutics is a biopharmaceutical company pioneering the discovery of a new class of medicines that directly target RNA. Arrakis is building a proprietary pipeline of RNA-targeted small molecule (rSM) medicines focused on cancer and genetically validated targets in other disease areas. The company brings together scientific leaders in RNA structure, chemistry and biology, along with a highly experienced management team and the backing of leading life sciences investors. The company is located in Waltham, Massachusetts. For more information, please visit www.arrakistx.com and engage with us on Twitter @ArrakisTx or on LinkedIn.

 

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Apple announces Worldwide Developers Conference dates, in-person event – CityNews Toronto

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Apple has announced their annual developers conference will take place June 10 through June 14.

The big summer event will be live-streamed, but some select developers have been invited to attend in-person events at Apple’s campus in Cupertino, California, on June 10.

The company typically showcases their latest software and product updates — including the iPhone, iPad, Apple Watch, AppleTV and Vision Pro headset — during a keynote address on the first day.

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Contributing to a drop in Apple’s stock price this year is concern it lags behind Microsoft and Google in the push to develop products powered by artificial intelligence technology. While Apple tends to keep its product development close to the vest, CEO Tim Cook signaled at the company’s annual shareholder meeting in February that it has been making big investments in generative AI and plans to disclose more later this year.

The week-long conference will have opportunities for developers to connect with Apple designers and engineers to gain insight into new tools, frameworks and features, according to the company’s announcement.

The Associated Press

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iPhone 16 Rumors Point to Action Button and New, Vertical Camera Layout – CNET

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The upcoming iPhone 16 and iPhone 16 Pro are still months away from their expected launch this fall, but a new set of images published online may give us a better sense of their potential features. Among the revelations, the iPhone 16 may include an action button, similar to the one on last year’s iPhone 15 Pro, and it may have redesigned cameras in a vertical stack.

AppleInsider published a series of photos it says show dummy 3D prints of the upcoming iPhone 16 and iPhone 16 Pro from an unnamed leaker. Aside from the action button and reworked cameras on the iPhone 16, AppleInsider also said its source found the iPhone 16 Pro to be “slightly larger” than its predecessor. Analysts had earlier said they expect the Pro model screens will grow somewhat.

Read more: iPhone 16: All the Major Rumors on Apple’s Next iPhone

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The new details suggest that a series of expected hardware updates are likely for this year’s new iPhones. Apple typically announces new iPhones around September, and the company tends to offer incremental upgrades to each new phone, introducing, over the period of several years, better cameras, screens and battery life, features that end up seeming like major upgrades when people get around to buying a new phone

Last year, Apple added a new titanium frame, action button and USB-C charging to its iPhone 15 Pro, which starts at $999. For its entry-level iPhone, Apple followed its well-worn strategy of trickling pro features down to the mainstream, adding the iPhone 14 Pro’s well-received Dynamic Island to the $799 iPhone 15, along with USB-C charging.

AppleInsider didn’t indicate whether its leaker had divined a reason for the iPhone 16’s shifted camera placements, but the two lenses will now reportedly be stacked one on top of the other, instead of diagonally. Apple has previously said it uses stacked lenses on the iPhone 15 Pro for spatial video capture, a key new technology the company highlighted as part of its $3,499 Apple Vision Pro headset, released in February.

Though AppleInsider’s leaks appear to confirm many previous rumors, not all renders and 3D prints are accurate, something the rumor blog notes itself in its report. Apple didn’t immediately respond to a request for comment about the veracity of the leaks.

Watch this: What Google Gemini AI on the iPhone Could Look Like

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I Took 600+ Photos With the iPhone 15 Pro and Pro Max. Look at My Favorites

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Leaked iPhone 16 dummy units hint at larger sizes and new buttons

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The iPhone 15 Pro Max, with a 6.7-inch screen
(Image credit: Future)

We’re already counting down to the arrival of the iPhone 16 series – most probably sometime in September – and a leak showing dummy units of the upcoming phones has revealed a few of the changes we can expect to see later this year.

These dummy units are usually based on supply chain information, and have various business uses – like helping case manufacturers get their wares ready for new phones before they’re launched, for example. In this case, the images were posted to Chinese social network Weibo, as spotted by MacRumors.

Perhaps the most interesting reveal from these blocks of plastic and metal is that they show the previously rumored increase in size for the iPhone 16 Pro and iPhone 16 Pro Max displays – up to 6.3 inches (from 6.1 inches) and 6.9 inches (from 6.7 inches) respectively.

That’s not a huge jump of course, but it does mean more screen space for apps and media. The bezels are apparently shrinking down to accommodate the larger screens, which means the increase in the physical size of these handsets is only a slight one.

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On the button

iPhone 16 dummy units leak

The next iPhones might look a bit like this, but less blue (Image credit: Weibo)

Further reveals from this leak match up with what we’ve heard before: that all four models are going to get the Action button that replaced the Ring/Silent switch on the 2023 Pro models, as well as a brand-new Capture button for getting more creative with photos.

Also of note is the redesigned rear camera module that we think is coming to the back of the iPhone 16 and iPhone 16 Plus. The new vertical, pill-shaped look has been leaked already, but this is more evidence that it’s on the way – taking us back to a design that’s more reminiscent of the iPhone 12, which came out in 2020.

As always with such rumors, be somewhat cautious about reading too much into the look of these dummy units. That said, as more and more similar leaks pile up, it becomes more likely that they’re based on accurate information.

The next big Apple date for your calendar is WWDC 2024 – its Worldwide Developers Conference starts on June 10, at which time we should hear much more about what’s coming this year with iOS 18 and Apple’s other software platforms.

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Freelance Contributor

Dave is a freelance tech journalist who has been writing about gadgets, apps and the web for more than two decades. Based out of Stockport, England, on TechRadar you’ll find him covering news, features and reviews, particularly for phones, tablets and wearables. Working to ensure our breaking news coverage is the best in the business over weekends, David also has bylines at Gizmodo, T3, PopSci and a few other places besides, as well as being many years editing the likes of PC Explorer and The Hardware Handbook.

Leaked iPhone 16 dummy units hint at larger sizes and new buttons

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