Base editing of the HBG promoter induces potent fetal hemoglobin expression with no detectable off-target mutations in human HSCs.

Reactivating silenced γ-globin expression through the disruption of repressive regulatory domains offers a therapeutic strategy for treating ß-hemoglobinopathies. Here, we used transformer base editor (tBE), a recently developed cytosine base editor with no detectable off-target mutations, to disrupt transcription-factor-binding motifs in hematopoietic stem cells. By performing functional screening of six motifs with tBE, we found that directly disrupting the BCL11A-binding motif in HBG1/2 promoters triggered the highest γ-globin expression. Via a side-by-side comparison with other clinical and preclinical strategies using Cas9 nuclease or conventional BEs (ABE8e and hA3A-BE3), we found that tBE-mediated disruption of the BCL11A-binding motif at the HBG1/2 promoters triggered the highest fetal hemoglobin in healthy and ß-thalassemia patient hematopoietic stem/progenitor cells while exhibiting no detectable DNA or RNA off-target mutations. Durable therapeutic editing by tBE persisted in repopulating hematopoietic stem cells, demonstrating that tBE-mediated editing in HBG1/2 promoters is a safe and effective strategy for treating ß-hemoglobinopathies.

[Study on the pollutants removal performance along the advanced treatment in tannery wastewater by O3-BAF].

A pilot-scale hybrid process of ozone and biological aerated filters (BAF) with the capacity of 36 t x d(-1) was applied for advanced treatment of the secondary biologically effluent from a dyeing and tannery park wastewater treatment plant. The pollutants removal performance along the height of different medias BAFs were investigated. The results showed that the average COD and color were 55.4 mg x L(-1) and 12.6 times at the height of 1500 mm in activated carbon BAF, and were 55.6 mg x L(-1) and 9.4 times at the height of 1 800 mm in composite BAF, both of the effluent at each height met the first level B criteria specified in the Discharge Standard of Pollutants for Municipal Wastewater Treatment Plant (GB 18918-2002). Along the height of ceramist BAF, the COD and color were seldom removed. In activated carbon BAF and composite BAF, COD and ammonia nitrogen were both greatly decreased at the height of 1 200 mm, then decreased slowly. The biomasses simultaneously reached the maximum at the height of 900 mm in activated carbon, composite and ceramist BAF, with the maxims of 30.69, 28.87 and 15.94 nmol x g(-1), respectively.