Ex vivo editing of human hematopoietic stem cells for erythroid expression of therapeutic proteins.

ABSTRACT: Targeted genome editing has a great therapeutic potential to treat disorders that require protein replacement therapy. To develop a platform independent of specific patient mutations, therapeutic transgenes can be inserted in a safe and highly transcribed locus to maximize protein expression. Here, we describe an ex vivo editing approach to achieve efficient gene targeting in human hematopoietic stem/progenitor cells (HSPCs) and robust expression of clinically relevant proteins by the erythroid lineage. Using CRISPR-Cas9, we integrate different transgenes under the transcriptional control of the endogenous α-globin promoter, recapitulating its high and erythroid-specific expression. Erythroblasts derived from targeted HSPCs secrete different therapeutic proteins, which retain enzymatic act

SUBMITTER: Pavani G 

PROVIDER: S-EPMC7391635 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature