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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.

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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Here is how to prepare your online accounts for when you die

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LONDON (AP) — Most people have accumulated a pile of data — selfies, emails, videos and more — on their social media and digital accounts over their lifetimes. What happens to it when we die?

It’s wise to draft a will spelling out who inherits your physical assets after you’re gone, but don’t forget to take care of your digital estate too. Friends and family might treasure files and posts you’ve left behind, but they could get lost in digital purgatory after you pass away unless you take some simple steps.

Here’s how you can prepare your digital life for your survivors:

Apple

The iPhone maker lets you nominate a “ legacy contact ” who can access your Apple account’s data after you die. The company says it’s a secure way to give trusted people access to photos, files and messages. To set it up you’ll need an Apple device with a fairly recent operating system — iPhones and iPads need iOS or iPadOS 15.2 and MacBooks needs macOS Monterey 12.1.

For iPhones, go to settings, tap Sign-in & Security and then Legacy Contact. You can name one or more people, and they don’t need an Apple ID or device.

You’ll have to share an access key with your contact. It can be a digital version sent electronically, or you can print a copy or save it as a screenshot or PDF.

Take note that there are some types of files you won’t be able to pass on — including digital rights-protected music, movies and passwords stored in Apple’s password manager. Legacy contacts can only access a deceased user’s account for three years before Apple deletes the account.

Google

Google takes a different approach with its Inactive Account Manager, which allows you to share your data with someone if it notices that you’ve stopped using your account.

When setting it up, you need to decide how long Google should wait — from three to 18 months — before considering your account inactive. Once that time is up, Google can notify up to 10 people.

You can write a message informing them you’ve stopped using the account, and, optionally, include a link to download your data. You can choose what types of data they can access — including emails, photos, calendar entries and YouTube videos.

There’s also an option to automatically delete your account after three months of inactivity, so your contacts will have to download any data before that deadline.

Facebook and Instagram

Some social media platforms can preserve accounts for people who have died so that friends and family can honor their memories.

When users of Facebook or Instagram die, parent company Meta says it can memorialize the account if it gets a “valid request” from a friend or family member. Requests can be submitted through an online form.

The social media company strongly recommends Facebook users add a legacy contact to look after their memorial accounts. Legacy contacts can do things like respond to new friend requests and update pinned posts, but they can’t read private messages or remove or alter previous posts. You can only choose one person, who also has to have a Facebook account.

You can also ask Facebook or Instagram to delete a deceased user’s account if you’re a close family member or an executor. You’ll need to send in documents like a death certificate.

TikTok

The video-sharing platform says that if a user has died, people can submit a request to memorialize the account through the settings menu. Go to the Report a Problem section, then Account and profile, then Manage account, where you can report a deceased user.

Once an account has been memorialized, it will be labeled “Remembering.” No one will be able to log into the account, which prevents anyone from editing the profile or using the account to post new content or send messages.

X

It’s not possible to nominate a legacy contact on Elon Musk’s social media site. But family members or an authorized person can submit a request to deactivate a deceased user’s account.

Passwords

Besides the major online services, you’ll probably have dozens if not hundreds of other digital accounts that your survivors might need to access. You could just write all your login credentials down in a notebook and put it somewhere safe. But making a physical copy presents its own vulnerabilities. What if you lose track of it? What if someone finds it?

Instead, consider a password manager that has an emergency access feature. Password managers are digital vaults that you can use to store all your credentials. Some, like Keeper,Bitwarden and NordPass, allow users to nominate one or more trusted contacts who can access their keys in case of an emergency such as a death.

But there are a few catches: Those contacts also need to use the same password manager and you might have to pay for the service.

___

Is there a tech challenge you need help figuring out? Write to us at onetechtip@ap.org with your questions.

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Google’s partnership with AI startup Anthropic faces a UK competition investigation

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LONDON (AP) — Britain’s competition watchdog said Thursday it’s opening a formal investigation into Google’s partnership with artificial intelligence startup Anthropic.

The Competition and Markets Authority said it has “sufficient information” to launch an initial probe after it sought input earlier this year on whether the deal would stifle competition.

The CMA has until Dec. 19 to decide whether to approve the deal or escalate its investigation.

“Google is committed to building the most open and innovative AI ecosystem in the world,” the company said. “Anthropic is free to use multiple cloud providers and does, and we don’t demand exclusive tech rights.”

San Francisco-based Anthropic was founded in 2021 by siblings Dario and Daniela Amodei, who previously worked at ChatGPT maker OpenAI. The company has focused on increasing the safety and reliability of AI models. Google reportedly agreed last year to make a multibillion-dollar investment in Anthropic, which has a popular chatbot named Claude.

Anthropic said it’s cooperating with the regulator and will provide “the complete picture about Google’s investment and our commercial collaboration.”

“We are an independent company and none of our strategic partnerships or investor relationships diminish the independence of our corporate governance or our freedom to partner with others,” it said in a statement.

The U.K. regulator has been scrutinizing a raft of AI deals as investment money floods into the industry to capitalize on the artificial intelligence boom. Last month it cleared Anthropic’s $4 billion deal with Amazon and it has also signed off on Microsoft’s deals with two other AI startups, Inflection and Mistral.

The Canadian Press. All rights reserved.

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Kuwait bans ‘Call of Duty: Black Ops 6’ video game, likely over it featuring Saddam Hussein in 1990s

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DUBAI, United Arab Emirates (AP) — The tiny Mideast nation of Kuwait has banned the release of the video game “Call of Duty: Black Ops 6,” which features the late Iraqi dictator Saddam Hussein and is set in part in the 1990s Gulf War.

Kuwait has not publicly acknowledged banning the game, which is a tentpole product for the Microsoft-owned developer Activision and is set to be released on Friday worldwide. However, it comes as Kuwait still wrestles with the aftermath of the invasion and as video game makers more broadly deal with addressing historical and cultural issues in their work.

The video game, a first-person shooter, follows CIA operators fighting at times in the United States and also in the Middle East. Game-play trailers for the game show burning oilfields, a painful reminder for Kuwaitis who saw Iraqis set fire to the fields, causing vast ecological and economic damage. Iraqi troops damaged or set fire to over 700 wells.

There also are images of Saddam and Iraq’s old three-star flag in the footage released by developers ahead of the game’s launch. The game’s multiplayer section, a popular feature of the series, includes what appears to be a desert shootout in Kuwait called Scud after the Soviet missiles Saddam fired in the war. Another is called Babylon, after the ancient city in Iraq.

Activision acknowledged in a statement that the game “has not been approved for release in Kuwait,” but did not elaborate.

“All pre-orders in Kuwait will be cancelled and refunded to the original point of purchase,” the company said. “We remain hopeful that local authorities will reconsider, and allow players in Kuwait to enjoy this all-new experience in the Black Ops series.”

Kuwait’s Media Ministry did not respond to requests for comment from The Associated Press over the decision.

“Call of Duty,” which first began in 2003 as a first-person shooter set in World War II, has expanded into an empire worth billions of dollars now owned by Microsoft. But it also has been controversial as its gameplay entered the realm of geopolitics. China and Russia both banned chapters in the franchise. In 2009, an entry in the gaming franchise allowed players to take part in a militant attack at a Russian airport, killing civilians.

But there have been other games recently that won praise for their handling of the Mideast. Ubisoft’s “Assassin’s Creed: Mirage” published last year won praise for its portrayal of Baghdad during the Islamic Golden Age in the 9th century.

The Canadian Press. All rights reserved.

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