Weekly Dose of Optimism #130
CT-179, Deep Research, NanoCas, Replit Agent, Go Birds
Hi friends 👋,
Happy Friday and welcome back to our 130th Weekly Dose of Optimism. Just a darn solid week here at the Weekly Dose — some good breakthrough scientific research and some important AI launches. We’ve come to expect these types of weeks, but we cannot take them for granted. Yes, the world is chaotic right now. But the world is also good. Got to remember that.
Let’s get to it.
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(1) OLIG2 mediates a rare targetable stem cell fate transition in sonic hedgehog medulloblastoma
Desai et al in Nature
Targeting this rare OLIG2-driven proliferative programme with a small molecule inhibitor, CT-179, dramatically attenuates early tumour formation and tumour regrowth post-therapy, and significantly increases median survival in vivo.
Some very good news to start the week. We may have discovered how to stop childhood tumors before they even begin to form.
Researchers found that the protein Olig2 is a key driver of medulloblastoma (a deadly pediatric brain cancer) growth by activating dormant cancer stem cells and turning them into rapidly dividing tumor cells. Blocking Olig2 with the drug CT-179 keeps these stem cells in a dormant state, preventing both initial tumor formation and relapse after treatment. In short, CT-179 might be able prevent pediatric brain tumors and also prevent them from coming back after treatment.
This approach is different from current therapies that target fast-growing tumor cells but fail to stop the cancer from returning. By focusing on the root of the disease—the stem cells that fuel tumor regrowth—this strategy could lead to more effective, long-lasting treatments for medulloblastoma. If you’re interested in a more in-depth breakdown, @vittorio has a full breakdown of the research on X.
From OpenAI
Deep research is a specialized AI capability designed to perform in-depth, multi-step research using data on the public web. It’s fine-tuned on the upcoming OpenAI o3 reasoning model and can autonomously search for and read information from diverse online sources. This enables it to create thorough, documented, and clearly cited reports on complex topics.
If you read the research paper from Nature above…good on ya. But if you’re anything like me, you likely copy + pasted the highly technical research into ChatGPT and prompted the model to give you a relatively short summary intended for an intelligent, but not expert audience. ChatGPT has been good at this type of summary work for a while. Now, it’s starting to get better at multi-step, complex research. Not just summarizing but, discovering, synthesizing, and reasoning about the content, and then it adapts its plan as it discovers more and more information. It can take over 5 minutes for deep research to return its answer as it works through the information and develops a thoughtful response. The response, then, is a fully cited research paper at the level of an expert researcher.
The use cases for deep research are plentiful — imagine an expert-level report on any topic generated in about 5 minutes. Not AI slop or excerpt from Wikipedia, but an in-depth, highly technical (if necessary), and thoughtfully reasoned research report. That’s useful in scientific research, advanced data analysis, investing, law, national security…or really any type of knowledge work that requires complex thinking. Ultimately, the goal for a tool like deep research is that it would be producing novel concepts and contributing to the research itself, but we’re not there yet. The current iteration is about discovering, synthesizing, and reasoning through existing information and presenting it in a way that can be understood.
Rauch et al
The compact size of NanoCas, in combination with robust nuclease editing, opens the door for single-AAV editing of non-liver tissues in vivo, including the use of newer editing modalities such as reverse transcriptase (RT) editing, base editing, and epigenetic editing.
What is this, CRISPR for ants?!
NanoCas is a newly designed tiny CRISPR system, about one-third the size of standard CRISPR (Cas9), making it small enough to fit into a single AAV delivery vector. An AAV delivery vector is a harmless virus used to deliver genetic material into cells for gene therapy. The big breakthrough with NanoCas is that its ability to fit into a single AAV is that it allows gene editing to reach muscle and heart tissues, not just the liver.
In monkeys, NanoCas successfully edited 30% of muscle cells, the first time a single-AAV CRISPR system has done this. It also fixed genes linked to cholesterol and muscular dystrophy in mice and monkeys, showing promise for treating muscle diseases. A modified version made NanoCas even more effective by improving how well it binds to DNA. NanoCas’ small size and strong performance could unlock potential gene editing treatments for muscle, the heart, and the brain. Lucas Harrington had a great breakdown of the research on X.
(4) Replit Agent
From Replit
Last week, we launched Replit Agent, our AI system that can create and deploy applications. Now, with only a few sentences and a few minutes, you can take an application from idea to deployment.
Make an app for that.
The gap between idea and execution keeps shrinking. This week, Not Boring portfolio company, Replit, launched Replit Agent. Basically you can prompt Replit Agent in as little as a few words to build an app for you and voilà you have the app. It takes your prompt and configures your development environment, installs dependencies, and executes code. If you’re not technical but have tried to code before, you’re likely familiar with the challenges of setting up first setting up the coding environment and actually deploying the code into production. Replit Agent makes all of that easy, and oh yeah, does the actually hard thing of writing the code as well. I believe even Packy (!) was able to spin up a pretty solid meditation app all while brushing his teeth.
The idea here to is lower the barrier to entry on coding as low as possible. Don’t know how to code? No problem. Don’t know how to set up a development environment? Why would you? In that same vein, Replit Agent is now available on mobile devices and completely free. You can be on the subway, or on the toilet, or walking to work and developing an app on your phone. And of course, in Replit fashion, you can always dig deeper from there — investigating the code, upgrading the design, customizing the UX, etc, etc.
(5) Super Bowl LIX
Blow the whistle!
It’s Super Bowl weekend and our hometown Philadelphia Eagles are once again competing for the Lombardi Trophy. I am surprised I was able to get any work done this week, frankly. I love football, I love the Eagles, and I love the city of Philadelphia. So this is a big week!
In a world that’s constantly changing, it’s rare to have a true interest that’s lasted now for over 20 years. It’s comforting and makes you feel grounded. That’s how many people feel about football, regardless of where you’re from. But there’s something about Philly and the Eagles that’s a bit different, at least in my very biased opinion.
Perhaps it’s due to the city itself: Philly is often overlooked and wedged between New York and DC. It’s one of the few big cities in our country where the people that live here are from here. It’s filled with history dating back to our country’s founding and prides itself on its blue collar work ethic. It’s racially and economically diverse, but on Sundays we all bleed green. Perhaps it’s the franchise: so close for so many years, but never quite able to push it over the goal line. It has ownership that embraces the city and invests in the team as if it were the city’s most valuable asset. It attracts talented players that know, going in, they’re playing for more than a paycheck. Perhaps it’s the players: this century, we’ve been blessed by big personalities like Donovan McNabb, Terrell Owens, and DeSean Jackson. Certified Football Guys like Jason Kelce, Chris Long, and Brandon Graham. And truly elite talents like Fletcher Cox, Lane Johnson, and Saquon Barkley.
I am lucky to be an Eagles fan. Go Birds.
Plus, speaking of Saquon:
When worlds collide. Our favorite finance operations platform, Ramp, and our favorite football player, Saquon Barkley, teamed up on this Super Bowl ad. This feels like micro ad targeting.
Packy here: if you love Saquon and Not Boring and you hate doing expenses, get your business on Ramp:
Ramp: The Official Business Card of Not Boring and Saquon Barkley. 🦅
We’ll be back in your inbox next week. In the meantime, Go Birds!
Thanks for reading,
Dan + Packy
God help me, I thought "sonic hedgehog" was a hallucination. Nope, that's what it's called.
superbowl time yaes