Ontology highlight
ABSTRACT:
SUBMITTER: Brendel C
PROVIDER: S-EPMC7150438 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Brendel Christian C Negre Olivier O Rothe Michael M Guda Swaroopa S Parsons Geoff G Harris Chad C McGuinness Meaghan M Abriss Daniela D Tsytsykova Alla A Klatt Denise D Bentler Martin M Pellin Danilo D Christiansen Lauryn L Schambach Axel A Manis John J Trebeden-Negre Helene H Bonner Melissa M Esrick Erica E Veres Gabor G Armant Myriam M Williams David A DA
Molecular therapy. Methods & clinical development 20200317
In this work we provide preclinical data to support initiation of a first-in-human trial for sickle cell disease (SCD) using an approach that relies on reversal of the developmental fetal-to-adult hemoglobin switch. Erythroid-specific knockdown of BCL11A via a lentiviral-encoded microRNA-adapted short hairpin RNA (shRNA<sup>miR</sup>) leads to reactivation of the gamma-globin gene while simultaneously reducing expression of the pathogenic adult sickle β-globin. We generated a refined lentiviral ...[more]