Today in @CellCellPress we report the use of prime editing to correct several mutations that cause alternating hemiplegia of childhood (AHC), a rare and devastating neurodevelopmental disorder, in patient-derived cells and in two mouse models. 1/10

A wonderful article by @DhruvKhullar on patients with progeria, the genetics behind this rare disease, and our ongoing efforts with PRF and @NIH to advance promising base editing outcomes in humanized progeria mice into a clinical trial.

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Data from the second human treated with a prime edited medicine: a 56-year-old male with chronic granulotamous disease (CGD) had his bone marrow prime edited to insert the missing GT in NCF1, restoring NADPH oxidase function in neutrophils (DHR positivity) several fold beyond the

RT @GrinsteinJ: Brilliant collab of @davidrliu (@broadinstitute / @Harvard) & Cat Lutz (@jacksonlab) shows that durable in vivo primed edit….

RT @EricTopol: One-shot prime genome editing ("CRISPR 3.0") of the brain in vivo corrected AHC, a rare genetic disorder, in the mouse model….

Research towards potential clinical use is underway. This work was co-led by @AlexanderASousa, @HoltSakai, and Markus Terrey and co-directed with Cat Lutz, in a wonderful collaboration of @broadinstitute, @jacksonlab, @RAREH0pe, @NorthwesternU, @MassGenBrigham, @UMassChan.

These results represent the first use of prime editing to rescue a neurological disease in animals, establish that in vivo postnatal intervention in AHC’s pathology is possible, and suggest the potential of a one-time prime editing treatment for AHC. (Photo:

In addition to the rescue of behavioral deficits, we also observed large long-term survival improvements in prime editor-treated AHC mice compared with their vehicle-treated counterparts. Indeed, the majority of all four PE-treated mouse cohorts were still alive at the time of

Prime editor-treated D801N (blue) and E815K (orange) AHC mice showed extensive rescue of multiple patient-relevant behavioral phenotypes, including rescue of rotarod-measured coordination to wild-type levels and near-elimination of trigger-induced seizures. 7/10

A single 1.1e11 vg/mouse P0 ICV injection of AAV9 encoding the prime editor into the brain resulted in up to 48% DNA and 73% mRNA correction in bulk cortex and rescued hippocampal Atp1a3 ATPase activity from ~50% to 77%–87% of wild-type activity in treated AHC mice. 6/10

Next we performed in vivo brain prime editing in two AHC mouse models (Markus Terrey, Cat Lutz, et al. @jacksonlab, PMID: 40381892). Both mouse models show key AHC features: motor/cognitive defects, paroxysmal attacks, reduced lifespan and weight, and Atp1a3 ATPase defects. 5/10

Genome-wide off-target analysis in patient-derived iPSCs detected minimal off-target editing, especially for PE and for the ABE8e-V106W or ABE7.10 variants of base editors. No off-target edits were found in exons, UTRs, splice junctions or promoters. 4/10

To directly address the genetic cause of AHC, we developed prime editing and base editing strategies to correct five ATP1A3 mutations, including the four most prevalent variants, with 43%–90% efficiency in AHC patient-derived iPSCs. 3/10

Most AHC cases are caused by mutations in ATP1A3, which encodes a sodium pump essential for neuron function. These mutations often have a dominant-negative effect; indeed, we observed that ATP1A3 gene addition in AHC mice did not improve behavioral phenotypes or survival. 2/10

RT @MichaelPacold: Just published: . Coenzyme Q10 (CoQ10) is critical for mitochondrial function and for controlli….

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RT @brkthroughprize: The Gene Editor: 2025 Breakthrough Prize winner David Liu introduces base editing and prime editing, the transformativ….

RT @broadinstitute: Gene editing pioneer @davidrliu discusses baby K.J. Muldoon, the first person treated with a customized gene editing th….

A preprint from @nataliyakosmyna and coworkers reports EEG evidence that writing using LLMs reduces neural connectivity and cognitive engagement compared to unaided writing or using standard search engines. Persistent use of LLMs weakened cognitive activation and impaired memory.

RT @LukeKoblan: 1/14.On behalf of the amazing team in @JswLab, we’re excited to share PEtracer ( a prime editing-ba….