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Series GSE145550 Query DataSets for GSE145550
Status Public on May 05, 2020
Title Cas12a base editors induce efficient and specific editing with low DNA damage response (DNA targeted sequencing)
Organisms Homo sapiens; Mus musculus
Experiment type Other
Summary The advent of base editors (BEs) holds a promising potential in correcting pathogenic-related point mutations to treat relevant diseases. Unexpectedly, Cas9 nickase (nCas9) derived BEs lead to DNA double-strand breaks, which can trigger unwanted cellular responses including a p53-mediated DNA damage response (DDR). Here, we showed that catalytically-dead-Cas12a (dCas12a) conjugated BEs induced no DNA break and minimally activated DDR proteins including H2AX, ATM, ATR and p53. We further developed a BEACON (Base Editing induced by human APOBEC3A and Cas12a without DNA break) system that fuses dCas12a to the engineered APOBEC3A with enhanced deamination efficiency and editing specificity. By using BEACON, efficient C-to-T editing was achieved at levels comparable to AncBE4max and only low levels of DDR and RNA off-target (OT) effects were triggered in mammalian cells. BEACON also induced in vivo base editing in mouse embryos and targeted C-to-T conversions were detected in F0 mice.
 
Overall design Examination of indels and base substitutions induced by the Cas12a base editors
 
Contributor(s) Yang L, Chen J, Liu Z, Yang B, Xiong Y, Wang X
Citation(s) 32492431
Submission date Feb 19, 2020
Last update date Aug 05, 2020
Contact name Li Yang
E-mail(s) [email protected]
Organization name Fudan University
Department Institutes of Biological Sciences
Street address 131 Dong-An Road
City Shanghai
ZIP/Postal code 200032
Country China
 
Platforms (5)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL19415 Illumina NextSeq 500 (Homo sapiens; Mus musculus)
Samples (248)
GSM4321121 rA1-dCas12a-BE:VEG-b, TET, S6, S3, RUN, RAG, PD1, DYR, DNM, CFT, CDK rep a
GSM4321122 rA1-dCas12a-BE:S4, RAG, FAN rep a; VEG-b, S6, RUN, DNM, CFT, CDK rep b
GSM4321123 rA1-dCas12a-BE:S4, PD1 rep b; S6, RUN, CFT rep c; VEG-a rep a
This SubSeries is part of SuperSeries:
GSE145552 Cas12a base editors induce efficient and specific editing with low DNA damage response
Relations
BioProject PRJNA607539
SRA SRP250019

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE145550_Indels.xls.gz 89.3 Kb (ftp)(http) XLS
GSE145550_RAW.tar 44.7 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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