Beeke Wienert

TL;DR: It is found that the major fetal globin gene repressors BCL11A and ZBTB7A directly bound to the sites at –115 and –200 bp, respectively, and introduced of naturally occurring HPFH-associated mutations into erythroid cells by CRISPR–Cas9 disrupted repressor binding and raised γ-globin gene expression.

TL;DR: This work introduces the naturally occurring Hereditary Persistance of Fetal Haemoglobin -175T>C point mutation associated with elevated fetal γ-globin into erythroid cell lines and shows that this mutation increases fetal globin expression through de novo recruitment of the activator TAL1 to promote chromatin looping of distal enhancers to the modified γ -globin promoter.

TL;DR: It is shown that the IVT gRNAs commonly used by many laboratories for RNP editing trigger a potent innate immune response that is similar to canonical immune-stimulating ligands, and removal of the 5’-triphosphate from g RNAs ameliorates inflammatory signaling and prevents the loss of viability associated with genome editing in hematopoietic stem cells.

TL;DR: Recent discoveries in hemoglobin were summarized, focusing on the influence of genome editing technologies, including CRISPR-Cas9, and emerging gene therapy approaches.