Genetic engineering meets hematopoietic stem cell biology for next-generation gene therapy

S Ferrari, E Valeri, A Conti, S Scala, A Aprile… - Cell Stem Cell, 2023 - cell.com
The growing clinical success of hematopoietic stem/progenitor cell (HSPC) gene therapy
(GT) relies on the development of viral vectors as portable" Trojan horses" for safe and …

Rationale and strategies for the development of safe and effective optimized AAV vectors for human gene therapy

A Srivastava - Molecular Therapy-Nucleic Acids, 2023 - cell.com
Recombinant adeno-associated virus (AAV) vectors have been, or are currently in use, in
332 phase I/II/III clinical trials in a number of human diseases, and in some cases …

Ex vivo prime editing of patient haematopoietic stem cells rescues sickle-cell disease phenotypes after engraftment in mice

KA Everette, GA Newby, RM Levine… - Nature biomedical …, 2023 - nature.com
Sickle-cell disease (SCD) is caused by an A· T-to-T· A transversion mutation in the β-globin
gene (HBB). Here we show that prime editing can correct the SCD allele (HBB S) to wild …

Chromothripsis as an on-target consequence of CRISPR–Cas9 genome editing

ML Leibowitz, S Papathanasiou, PA Doerfler… - Nature …, 2021 - nature.com
Genome editing has therapeutic potential for treating genetic diseases and cancer.
However, the currently most practicable approaches rely on the generation of DNA double …

High-efficiency transgene integration by homology-directed repair in human primary cells using DNA-PKcs inhibition

S Selvaraj, WN Feist, S Viel, S Vaidyanathan… - Nature …, 2024 - nature.com
Therapeutic applications of nuclease-based genome editing would benefit from improved
methods for transgene integration via homology-directed repair (HDR). To improve HDR …

Choice of template delivery mitigates the genotoxic risk and adverse impact of editing in human hematopoietic stem cells

S Ferrari, A Jacob, D Cesana, M Laugel, S Beretta… - Cell Stem Cell, 2022 - cell.com
Long-range gene editing by homology-directed repair (HDR) in hematopoietic
stem/progenitor cells (HSPCs) often relies on viral transduction with recombinant adeno …

Efficient gene editing of human long-term hematopoietic stem cells validated by clonal tracking

S Ferrari, A Jacob, S Beretta, G Unali, L Albano… - Nature …, 2020 - nature.com
Targeted gene editing in hematopoietic stem cells (HSCs) is a promising treatment for
several diseases. However, the limited efficiency of homology-directed repair (HDR) in …

Genome editing of HBG1 and HBG2 to induce fetal hemoglobin

JY Métais, PA Doerfler, T Mayuranathan… - Blood …, 2019 - ashpublications.org
Induction of fetal hemoglobin (HbF) via clustered regularly interspaced short palindromic
repeats/Cas9–mediated disruption of DNA regulatory elements that repress γ-globin gene …

Diverse approaches to gene therapy of sickle cell disease

SL White, K Hart, DB Kohn - Annual review of medicine, 2023 - annualreviews.org
Sickle cell disease (SCD) results from a single base pair change in the sixth codon of the β-
globin chain of hemoglobin, which promotes aggregation of deoxyhemoglobin, increasing …

Correction of β-thalassemia by CRISPR/Cas9 editing of the α-globin locus in human hematopoietic stem cells

G Pavani, A Fabiano, M Laurent, F Amor… - Blood …, 2021 - ashpublications.org
Abstract β-thalassemias (β-thal) are a group of blood disorders caused by mutations in the β-
globin gene (HBB) cluster. β-globin associates with α-globin to form adult hemoglobin (HbA …