IGF2BP1 revealed as a double agent* hemoglobin switcher! How this heterochronic RBP both inhibits BCL11A (thru HIC2) & directly binds + supports the fetal globin transcript: ashpublications.org/blood/articl... Led by fantastic Steve Coyne. *Scott Peslak blurb: ashpublications.org/blood/articl...

Direct and indirect regulation of fetal globin transcript by the RNA-binding protein IGF2BP1

Key PointsThe RBP regulates fetal hemoglobin directly through posttranscriptional control and indirectly via BCL11A.IGF2BP1 binding to a stop codon–proxima

ashpublications.org

Inspired by Gibson cloning, we describe prime assembly, now published, for in cellulo targeted integration of gene-sized DNA fragments using prime editing. www.nature.com/articles/s41...

In this piece, my mentor Stu Orkin and I (1) marvel at prime editing—discovery to disease correction for 2 patients after just 6 yr—wow Liu, Anzalone, Gori, Malech et al! & (2) consider the challenges to deliver genetic medicine’s promise for 2^n patients www.nejm.org/doi/full/10....

Genetic Medicine — Primed and Ready | NEJM

Immunodeficiency chronic granulomatous disease (CGD) is a rare disorder characterized by defects in a multiprotein complex that generates superoxide in phagocytic cells.1 Recurrent infections and f...

nejm.org

@sebastien-levesque.bsky.social and I review therapeutic genome editing for inherited blood disorders rdcu.be/ewcZ3. We cover CRISPR, patient journey, DNA repair, patient access, genotoxicity, hemoglobinopathies, delivery, bone marrow failure, coselection, immunodeficiency, and more.

CRISPR-based therapeutic genome editing for inherited blood disorders

Nature Reviews Drug Discovery - CRISPR-based technologies provide a diverse set of tools to correct pathogenic mutations. This Review describes the promise and the challenges of genome editing...

rdcu.be

Excited to share our latest where we describe a gene editing method termed prime assembly that enables RNA programmable targeted integration of gene-sized DNA sequences in nondividing cells without dsDNA or nuclease-driven DSBs. See thread by incomparable @Seb. Also complementary work Sontheimer/Xue

Sébastien Levesque@sebastien-levesque.bsky.social · last yr.

I’m thrilled to share our latest preprint! Inspired by isothermal Gibson assembly cloning, we wondered whether we could assemble and integrate DNA sequences at a specific genomic locus in human cells. A thread (1/7) www.biorxiv.org/content/10.1...

In @nature.com we describe the use of scalable #proteinengineering & #machinelearning to predict millions of bespoke CRISPR enzymes, offering safer & more efficient genome editing tools 🧬🖥️ @rachelsilverstein9.bsky.social @mgbresearch.bsky.social @harvardmed.bsky.social www.nature.com/articles/s41...

New paper from my lab! Elevated mitochondrial membrane potential is a therapeutic vulnerability in Dnmt3a-mutant clonal hematopoiesis: rdcu.be/eh1Nb Complementary to new work from Steven Chan & @georgevassiliou.bsky.social as described by @goodell-lab.bsky.social: www.nature.com/articles/d41...

Age-related blood condition counteracted with a common diabetes drug

Metformin could reduce people’s risk of certain age-associated blood cancers, but more work is needed to identify who is likely to benefit.

nature.com

Francis Collins, the NIH Director for 12 years, led the Human Genome Project and other NIH efforts for 32 years, resigned today. Key words from his resignation letter www.nytimes.com/2025/03/01/u...