Geoff Howe

Delighted to have successfully defended my PhD last month! We built DNA clearing HEK cells and designed AAV protein variants to study their function and improve AAV manufacturing! Huge thanks to my PI @GenePlumber, everyone @UCLBiochemEng1, examiners @alanlparker & @pauldalby!

To understand hT7-AAV tropism, we performed a genome wide CRISPR screen on human primary T cells and excitingly, identified CD7, a T/NK cell marker, as a critical transduction factor. Huge effort @PL_Bernard @HuiCharlotte @gabbykimmerly

I am so excited to share our new paper in @Nature: the first programmable, site-specific integration of a large DNA payload into T cells in vivo. A single IV injection results in therapeutic levels of TRAC-targeted CAR T cells in multiple models. #Ack1" target="_blank" rel="nofollow noopener">nature.com/articles/s4158… a 🧵

Below is the story of the first patient treated with a prime-edited therapeutic, developed by @PrimeMedicine in a trial led by Dr. Élie Haddad and his team at CHU Sainte-Justine. This teenager suffered from chronic granulomatous disease (CGD), an immunodeficiency, and now—10 months after treatment—the patient is healthy, stable, and living with a functioning immune system. Tracy Attebury, whose story was previously told by @ginakolata @nytimes, was the second patient treated with a prime-edited therapeutic. cihr-irsc.gc.ca/e/54638.html

Engineered AAV Capsids with Enhanced Extracellular Vesicle Loading via Rational Design and Directed Evolution biorxiv.org/content/10.648… #biorxiv_synbio

RFdiffusion3 now available! De novo protein design against any molecule Try it on @tamarindbio today RF3 shows success in designing de novo proteins against all-atom targets, including proteins, DNA and small molecules with diverse applications.

Today, we report a method for design of active enzymes, RFdiffusion2, in @naturemethods. For the first time, we are able to design enzymes with native-range catalytic activity. We also are releasing our next frontier model, RFdiffusion3, code 👇

The first two lines of this paper illustrate quite how important this discovery is: “Approximately half the worldwide population is at risk for dengue. No antiviral prophylaxis or treatment options are available.”

Excited to present the first major work after starting our lab at Stanford and the Arc this year: CRISPR-All, a unified genetic perturbation language for programming any major type of genetic perturbation simultaneously, in any combination, at genome scale, in human cells.

For visual learners like me, this is probably the best feature of Nano Banana Pro I was reading a paper on Structural and thermodynamics stability of T4 Lysozyme mutants

A preprint out today from Arc Innovation Investigator Theo Roth, @AustinMHartman, @Oli_TN, and colleagues introduces CRISPR All–a unified programming language for editing human cells across all major genetic perturbation types at once.

@nablabio @AdrianoAguzzi there are no known antagonists of a certain unnamed GPCR which is massively expressed in the brain and is a receptor for PrP…

Today we’re thrilled to announce JAM-2 — the first AI model capable of generating drug-quality antibodies straight from the computer, with industry-leading success rates. > Drug-like affinities: Picomolar to single-digit nanomolar antibody binders for half of 26 targets while testing <45 designs each. > Unlocking hard targets: Up to 11% success rate for direct on-cell GPCR binders; top antibody hits in the single-digit nanomolar range. > Unprecedented epitope breadth: JAM-2 routinely designed antibodies that hit 30–70% of user-defined epitopes, now enabling intentional design of biology — not chance discovery. > Drug-like developability: Over 50% of antibody designs passed core industry developability criteria with zero optimization. > Massive leverage: A four-person team prosecuted 16 targets in parallel in < 1 month. JAM-2 is the first de novo antibody design capability ready for front-line use in drug discovery, matching or surpassing traditional discovery approaches. We’re already deploying JAM-2 with multiple large pharma partners and seeing excellent results. If you’re interested in partnering on molecule development or accessing JAM-2, contact bd@nabla.bio. Read more in our whitepaper (link below)

The title alone would tempt me to apply and do it all again (speaking as a postdoc with a PhD from the Nesbeth lab)! A fantastic opportunity!!

Dave Ricks has been at @EliLillyandCo for 20% of its 150-year history. He came to the pub, poured his own Guinness, and gave us a 2-hour state of the pharma union: drug prices, clinical trials, patent clocks, the rise of generics, Chinese peptides, compounding pharmacies, the US healthcare system, and how the broad success of GLP-1s have transformed Lilly's business. If you've never heard Dave speak before, you're in for a treat. Timestamps: 00:00 Intro 05:08 Making R&D decisions 10:11 Clinical trials 24:59 Drug pricing 32:43 Stimulating more R&D 45:16 Pros and cons of US healthcare 58:20 New pharma business models 01:05:53 Stripe + enterprises 01:07:00 China 01:16:31 Generics 01:22:37 GLP-1s 1:37:43 r/Peptides 01:41:25 LillyDirect 01:46:35 Why do investors love LLY?

This is a fascinating interview – I've listened twice now, here's the 5 most interesting things 1. Inflammation drops fast on GLP1s (before weight loss) - one theory is that overeating itself may be inflammatory

Papers like this which demonstrate that alpha synuclein can act potently as prions, are exactly why you need to have proportionate safety measures in labs doing this kind of work. If you work on this and don’t have safety measures ask why! Great paper btw. nature.com/articles/s4158…

Today I had lunch with twelve young Irish people -- a wonderful bunch in their early 20s working on rockets, biotech, software/AI, etc. I enquired about whether any were planning on leaving Ireland over the next 3 years. All hands but one went up. I asked the holdout why he was staying; he clarified that he was also going to leave, just not in the next three years. Mobility is a wonderful thing, but it feels worrisome if everyone in such a group concludes that they ought to emigrate. This desire seems to generalize. A 2023 study suggested that more young people want to leave Ireland than any other EU country.

Something Gotham-esque about Hamburg tonight with the fog!

A grey day in Hamburg spent discussing all things virology and CRISPR screening at the DEFENDER symposium - an EU funded consortium on a mission to identify new targets and develop new therapies against high priority viruses.

Repeated head trauma causes neuron loss and inflammation in young athletes: nature.com/articles/s4158…

🔬 Funded PhD 'Engineering self-regulating CAR-T cells' #SynBio #EngBio #iGEM2025 Work across mammalian synthetic biology & mathematical modelling. ⏰ Apply by 1pm UK, 5 Jan 2026 Project details: ucl-epsrc-dtp.github.io/2026-27-projec… Project application portal: ucl.ac.uk/epsrc-doctoral…