Zhang, X., Zhu, B., Chen, L. et al. Dual base editor catalyzes both cytosine and adenine base conversions in human cells. Nature Biotechnology (2020).
Although base editors are useful tools for precise genome
editing, current base editors can only convert either adenines
or cytosines. We developed a dual adenine and cytosine base
editor (A&C-BEmax) by fusing both deaminases with a Cas9
nickase to achieve C-to-T and A-to-G conversions at the same
target site. Compared to single base editors, A&C-BEmax’s
activity on adenines is slightly reduced, whereas activity on
cytosines is higher and RNA off-target activity is substan-
Yang L, Wang L, Huo Y, et al. Amelioration of an Inherited Metabolic Liver Disease through Creation of a De Novo Start Codon by Cytidine Base Editing [published online ahead of print, 2020 May 7].
Correction to: Increasing targeting scope
of adenosine base editors in mouse and rat
embryos through fusion of TadA deaminase
with Cas9 variants
Zhang X, Chen L, Zhu B, et al. Increasing the efficiency and targeting range of cytidine base editors through fusion of a single-stranded DNA-binding protein domain [published online ahead of print, 2020 May 11]. Nature Cell Biology. 2020.
Cytidine base editors are powerful genetic tools that catalyse cytidine to thymidine conversion at specific genomic loci,
and further improvement of the editing range and efficiency is critical for their broader applications. Through insertion of a
non-sequence-specific single-stranded DNA-binding domain from Rad51 protein between Cas9 nickase and the deaminases,
serial hyper cytidine base editors were generated with substantially increased activity and an expanded editing window
towards the protospacer adjacent motif in both cell lines and mouse embryos. Additionally, hyeA3A-BE4max selectively cata-
lysed cytidine conversion in TC motifs with a broader editing range and much higher activity (up to 257-fold) compared with
eA3A-BE4max. Moreover, hyeA3A-BE4max specifically generated a C-to-T conversion without inducing bystander mutations in
the haemoglobin gamma gene promoter to mimic a naturally occurring genetic variant for amelioration of β-haemoglobinopathy,
suggesting the therapeutic potential of the improved base editors.
Wang L, Li L, Ma Y, Hu H, et al. Reactivation of γ-globin Expression through Cas9 or Base Editor to Treat β-Hemoglobinopathies. Cell Research, 2020,1
Mutations in the β-globin gene, the essential component of adult hemoglobin (HbA; α2β2), results in either a production of aberrant sickle hemoglobin (HbS) leading to sickle cell disease (SCD) or an insufficient β-globin synthesis leading to β-thalassemia. These two major forms of β-hemoglobinopathies cause impaired erythropoiesis and life-threatening anemia. Clinical evidence has suggested that re-activation of fetal γ-globin (HBG) gene expression which is normally silenced after birth by certain genetic mutations can ameliorate the clinical course of β- hemoglobinopathies 1, 2. In β-thalassemia, elevated levels of fetal γ-globin interact with α-globin to form fetal hemoglobin (HbF; α2γ2) restoring the α/β-like globin ratio and in SCD the γ-globin reduces HbS polymerization.