This study identifies the MLL1 complex as a regulator of fetal hemoglobin repression and shows that targeting MEN1 or KMT2A increases fetal hemoglobin expression in erythroid cells.

bioRxiv · Mar 24, 2025 · PreprintDevelopmental Biology

Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells

Jing Zeng, My Anh Nguyen, Pengpeng Liu, Lucas Ferreira da Silva, Sébastien Levesque, Linda Yingqi Lin, David G. Justus, Karl Petri, Kendell Clement, Shaina N. Porter, Archana Verma, Nola R. Neri, Tolulope O. Rosanwo, Marioara-Felicia Ciuculescu, Daniela Abriss, , Daniel E. Bauer

This study shows that gene editing of HSCs without ex vivo culture reduces genotoxicity while maintaining therapeutic efficacy for beta-hemoglobinopathy treatment.

Cell stem cell · Dec 12, 2024Peer-reviewedGenetics

Development and IND-enabling studies of a novel Cas9 genome-edited autologous CD34+ cell therapy to induce fetal hemoglobin for sickle cell disease

Varun Katta, Kiera O’Keefe, Yichao Li, Thiyagaraj Mayuranathan, Cícera Regina Lazzarotto, Rachael K. Wood, Rachel M. Levine, Alicia Powers, Kalin D. Mayberry, Garret Manquen, Yu Yao, Jingjing Zhang, Yoonjeong Jang, Nikitha Nimmagadda, Erin Dempsey, , Shengdar Q. Tsai

This study develops a genome-edited autologous CD34+ cell therapy to induce fetal hemoglobin for sickle cell disease, showing efficient editing, therapeutic HbF levels, and no off-target effects.

Molecular Therapy · Jul 30, 2024Peer-reviewedGenomics

Gene replacement of α-globin with β-globin restores hemoglobin balance in β-thalassemia-derived hematopoietic stem and progenitor cells

M. Kyle Cromer, Joab Camarena, Renata M. Martin, Benjamin J. Lesch, Christopher A. Vakulskas, Nicole M. Bode, Gavin Kurgan, Michael A. Collingwood, Garrett R. Rettig, Mark A. Behlke, Viktor T. Lemgart, Yankai Zhang, Ankush Goyal, Feifei Zhao, Ezequiel Ponce, , Matthew Hebden Porteus

This study replaces the HBA1 gene with HBB in β-thalassemia-derived HSPCs using CRISPR, normalizing globin ratios and restoring functional hemoglobin.

Nature Medicine · Mar 18, 2021Peer-reviewedMolecular Biology

Robust generation of erythroid and multilineage hematopoietic progenitors from human iPSCs using a scalable monolayer culture system

Juan Pablo Ruíz, Guibin Chen, Juan J. Haro‐Mora, Keyvan Keyvanfar, Chengyu Liu, Jizhong Zou, Jeanette K. Beers, Hanan Bloomer, Husam Qanash, Naoya Uchida, John F. Tisdale, Manfred Boehm, André Larochelle

This study develops a scalable monolayer culture system for generating erythroid and multilineage hematopoietic progenitors from human iPSCs, showing limited HSC engraftment potential.

Stem Cell Research · Oct 15, 2019Peer-reviewedDevelopmental Biology

Aberrant Clonal Hematopoiesis Following Lentiviral Transduction of HSPC in a Rhesus Macaque

Diego A. Espinoza, Xing Fan, Di Yang, Stefan Cordes, Lauren L. Truitt, Katherine R. Calvo, Idalia M. Yabe, Selami Demirci, Kristin J. Hope, So Gun Hong, Allen E. Krouse, Mark E. Metzger, Aylin C. Bonifacino, Rong Lu, Naoya Uchida, , Cynthia E. Dunbar

This paper reports a case of clonal hematopoiesis in a rhesus macaque following lentiviral transduction of HSPC with a strong retroviral promoter, leading to gene overexpression and aberrant splicing.

Molecular Therapy · Apr 9, 2019Peer-reviewedMolecular Biology