Preclinical Evaluation of a Novel Lentiviral Vector Driving Lineage-Specific BCL11A Knockdown for Sickle Cell Gene Therapy
Christian Brendel, Olivier Nègre, Michael Rothe, Swaroopa Guda, Geoff Parsons, Chad E. Harris, Meaghan McGuinness, Daniela Abriss, Alla V. Tsytsykova, Denise Klatt, Martin Bentler, Danilo Pellin, Lauryn Christiansen, Axel Schambach, John Manis, Hélène Trebeden‐Negre, Melissa Bonner, Erica B. Esrick, Gábor Veres, Myriam Armant, David A. Williams
Abstract
immortalization assays, which are designed to measure vector-mediated genotoxicity, showed no increased immortalization compared with mock-transduced cells. Together these data demonstrate that BCH-BB694 LVV is non-toxic and efficacious in preclinical studies, and can be generated at a clinically relevant scale in a GMP setting at high titer to support clinical testing for the treatment of SCD.
Topics & Concepts
Gene knockdownViral vectorGenetic enhancementFetal hemoglobinIn vivoHemoglobinBiologyGlobinVector (molecular biology)CRISPRCancer researchSmall hairpin RNAGeneMedicineMolecular biologyGeneticsFetusBiochemistryPregnancyRecombinant DNAHemoglobinopathies and Related DisordersPrenatal Screening and DiagnosticsParvovirus B19 Infection Studies