Project description:Techniques for exclusion of exons from mature transcripts have been applied as gene therapies for treating many different diseases. Since exon skipping has been traditionally accomplished using technologies that have a transient effect, it is particularly important to develop new techniques that enable permanent exon skipping. We have recently demonstrated that this can be accomplished using cytidine base editors for permanently disabling the splice acceptor of target exons. We now demonstrate the application of adenine-deaminase base editors to disrupt the conserved adenosine within splice acceptor sites for programmable exon skipping. We also demonstrate that by altering the amino acid sequence of the linker between the adenosine deaminase domain and the Cas9 nickase or by coupling the adenine base editor with a uracil glycosylase inhibitor, the DNA editing efficiency and exon skipping rates improve significantly. Finally, we developed a split base editor architecture compatible with adeno-associated viral packaging. Collectively, these results represent significant progress towards permanent in vivo exon skipping through base editing and, ultimately, a new modality of gene therapy for the treatment of genetic diseases.
Project description:To characterize the PTI response of tomato and the effect of the delivery of a subset of effectors, we performed an RNA-seq analysis of tomato Rio Grande prf3 leaves challenged with either the flgII-28 peptide or the following bacterial strains: Agrobacterium tumefaciens GV2260, Pseudomonas fluorescens 55, Pseudomonas putida KT2440, Pseudomonas syringae pv. tomato (Pst) DC3000, Pst DC3000 deltahrcQ-U deltafliC and Pst DC3000 deltaavrPto deltaavrPtoB. NOTE: Samples in SRA were assigned the same sample accession. This is incorrect as there are different samples, hence âSource Nameâ was replaced with new values. Comment[ENA_SAMPLE] contains the original SRA sample accessions.
Project description:We used an adenine base editor to target the translation start site and mRNA splicing site of Camk2d in order to knock out CaMKIIδ. We found that editing the 5' splice site of intron 7 can lead to premature translation termination, effectively knocking out CaMKIIδ.
Project description:We used an adenine base editor to target the translation start site and mRNA splicing site of Camk2d in order to knock out CaMKIIδ. We found that editing the 5' splice site of intron 7 can lead to premature translation termination, effectively knocking out CaMKIIδ.
Project description:Adenine and cytosine base editors (ABEs and CBEs) represent a new genome editing technology that allows the programmable installation of A-to-G or C-to-T alterations on DNA. We engineered Streptococcus pyogenes Cas9-based adenine and cytosine base editor (SpACE) that enables efficient simultaneous introduction of A-to-G and C-to-T substitutions in the same base editing window on DNA.
2020-07-02 | GSE137411 | GEO
Project description:ABE-Ultramax for high-efficiency biallelic adenine base editing
| PRJNA1118438 | ENA
Project description:ABE-Ultramax for high-efficiency biallelic adenine base editing