CRISPR-Cas9 Editing of the <i>HBG1</i> and <i>HBG2</i> Promoters to Treat Sickle Cell Disease.

ABSTRACT:

Background

Sickle cell disease is caused by a defect in the β-globin subunit of adult hemoglobin. Sickle hemoglobin polymerizes under hypoxic conditions, producing deformed red cells that hemolyze and cause vaso-occlusion that results in progressive organ damage and early death. Elevated fetal hemoglobin levels in red cells protect against complications of sickle cell disease. OTQ923, a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-edited CD34+ hematopoietic stem- and progenitor-cell (HSPC) product, has a targeted disruption of the HBG1 and HBG2 (γ-globin) gene promoters that increases fetal hemoglobin expression in red-cell progeny.

Methods

We performed a tiling CRISPR-Cas9 screen of the HBG1 and HBG2 promoters by electr

SUBMITTER: Sharma A 

PROVIDER: S-EPMC10947132 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature