Replying to @plasmidsaurus
Insert missing. Nanopore confirmed betrayal
Gabriel M. C. Longo retweeted
Today in @Nature we introduce INSTALL, which bypasses mammalian DNA immune sensing to enable non-viral DNA integration with recombinases—a step toward safe, scalable, and mutation-agnostic genome editing. 🧬 🧵(1/13)
nature.com/articles/s41586-0…
@BKleinstiver @CGM_MGH @MassGeneralNews @harvardmed
Gabriel M. C. Longo retweeted
New Article! Multilevel characterization of genome editor nuclease activity with BreakTag bit.ly/4o0SFOD
Read our original publication in Nature Biotechnology here: nature.com/articles/s41587-0…
Read our Nature Protocols publication here: nature.com/articles/s41596-0…
ReadCube: rdcu.be/eQKQX
Major thanks to Sergi Sayols. and @RoukosVassilis for their invaluable contribution to this work!
Finally, we demonstrate how users can leverage XGScission, a machine-learning model trained with BreakTag data to predict scission profiles from target sequences. We also provide a pre-trained SpCas9 model for predicting profiles of sequences not seen during training.
HiPlex BreakTag enables targeting thousands of sites in the human genome, generating datasets suitable for machine-learning training. BreakTag data are analyzed with BreakinspectoR, a dedicated pipeline for off-target discovery and nuclease characterization.
As the field advances toward engineering Cas9 enzymes for clinical applications, we believe there is a significant need for tools that can comprehensively characterize these enzymes within a single assay. BreakTag can be performed in two major modes: singleton and HiPlex.
We previously used BreakTag to study factors shaping blunt and staggered Cas9 cuts, finding that sequence context influence scission profiles. Staggered ends drive precise templated insertions that can correct 1nt deletions, and Cas9 variants enable tailored cleavage types. +
Today we report in Nature Protocols a comprehensive protocol on BreakTag, our suite of tools for the characterization of CRISPR nucleases across multiple dimensions: activity, specificity, PAM usage and scission profile. +
nature.com/articles/s41596-0…
Gabriel M. C. Longo retweeted
.@SecKennedy - thank you so much for your broad support for gene editing and gene therapies as well as recognizing the importance of Baby KJ’s story and the potential that CRISPR base editing therapies hold for patients with severe genetic diseases. I’m thrilled you have publicly recognized the Herculean efforts that made KJs therapy possible, from the physicians @CHOP like @kiranmusunuru and Rebecca Ahrens-Nicklas to the technological innovation in @davidrliu and @BKleinstiver labs, and especially the coordination and cooperation of the regulators @US_FDA that made this possible.
The gene editing medicine KJ received, a CRISPR adenine base editor was invented and developed in @davidrliu lab @Harvard with government grants from the NIH. This life-saving medicine, and so many future technologies, could not and will not be possible without government grants such as the one that supported this work, but are now shut off by this administration.
So PLEASE ask this administration to stop attacking our academic institutions and restore government funding to @Harvard (where again, KJ’s medicine was created!!) We cannot have stories like KJ’s without full and unwavering support from the US government.
Please help, please.
Thursday morning, I had the privilege of speaking with the Muldoon family, whose 10-month-old son, baby KJ, was discharged Wednesday from @ChildrensPhila. Baby KJ was diagnosed with a rare urea cycle disorder and received a first-of-its-kind personalized CRISPR gene-editing therapy—customized specifically for his unique mutation.
Thanks to the extraordinary expertise and compassion of the team at CHOP and the researchers who developed this pioneering treatment, baby KJ now has a second chance at life. The Muldoon family’s courage is nothing short of inspiring, and I offer my deepest gratitude to everyone at CHOP and beyond who made this medical milestone possible.
This isn’t just a medical success story—it’s a powerful glimpse into the future of personalized medicine.
I remain firmly committed to working with @NIHDirector_Jay, @DrMakaryFDA, @DrOzCMS, and others to ensure that:
• HHS continues to invest in cutting-edge research that drives breakthrough therapies
• Our regulatory frameworks keep pace with rapid innovation
• No family is ever denied access to life-saving treatments because of cost
Breakthroughs like this are why we do the work.
Gabriel M. C. Longo retweeted
Really nice characterization of Cas9 DSBs in human gDNA, with thorough off-target profiling and modeling of DSB outcomes for different guides. From @genomewizard @VassilisRozanas
The genome-wide landscape of Cas-induced double-strand breaks and end structures is profiled at nucleotide resolution go.nature.com/44DO2Cc
rdcu.be/ekKtv
Gabriel M. C. Longo retweeted
The genome-wide landscape of Cas-induced double-strand breaks and end structures is profiled at nucleotide resolution go.nature.com/44DO2Cc
rdcu.be/ekKtv
Gabriel M. C. Longo retweeted
In @nature we describe the use of scalable #proteinengineering & #machinelearning to predict millions of bespoke CRISPR-Cas9 enzymes, offering safer & more genome editing tools. 🧬🖥️
@RachelSilvers11 @CGM_MGH @MGH_RI @MassGeneralNews @harvardmed
nature.com/articles/s41586-0…









