Publications by authors named "Karin Tenglin"
Down-regulation of BCL11A protein reverses the fetal (HbF, αγ) to adult (HbA, αβ) hemoglobin switch and is exploited in gene-based therapy for hemoglobin disorders. Because of reliance on ex vivo cell manipulation and marrow transplant, such therapies cannot lessen disease burden. To develop new small-molecule approaches, we investigated the state of BCL11A protein in erythroid cells.
View Article and Find Full Text PDFTranscription factors (TFs) control numerous genes that are directly relevant to many human disorders. However, developing specific reagents targeting TFs within intact cells is challenging due to the presence of highly disordered regions within these proteins. Intracellular antibodies offer opportunities to probe protein function and validate therapeutic targets.
View Article and Find Full Text PDFArticle Synopsis
- Proximity-based strategies for degrading proteins show promise in medicine, but traditional methods are limited to proteins with existing small molecule ligands.
- Researchers used yeast surface display of synthetic nanobodies to find a ligand specifically targeting BCL11A, which represses fetal globin gene transcription.
- By fusing the nanobody with a miniature protein and an E3 adaptor, they created a degrader that reduces BCL11A levels in erythroid precursor cells, boosting fetal hemoglobin expression and offering a novel approach to treat sickle cell disease and β-thalassemia.