General Information
- Project ID
- OEP000277
- Project Name
- Off-target RNA mutation induced by DNA base editing
- Description
- Recently developed DNA base editing methods enable the direct generation of desired point mutations in genomic DNA without generating any double-strand breaks1,2,3, but the issue of off-target edits has limited the application of these methods. Although several previous studies have evaluated off-target mutations in genomic DNA4,5,6,7,8, it is now clear that the deaminases that are integral to commonly used DNA base editors often bind to RNA9,10,11,12,13. For example, the cytosine deaminase APOBEC1—which is used in cytosine base editors (CBEs)—targets both DNA and RNA12, and the adenine deaminase TadA—which is used in adenine base editors (ABEs)—induces site-specific inosine formation on RNA9,11. However, any potential RNA mutations caused by DNA base editors have not been evaluated. Adeno-associated viruses are the most common delivery system for gene therapies that involve DNA editing; these viruses can sustain long-term gene expression in vivo, so the extent of potential RNA mutations induced by DNA base editors is of great concern14,15,16. Here we quantitatively evaluated RNA single nucleotide variations (SNVs) that were induced by CBEs or ABEs. Both the cytosine base editor BE3 and the adenine base editor ABE7.10 generated tens of thousands of off-target RNA SNVs. Subsequently, by engineering deaminases, we found that three CBE variants and one ABE variant showed a reduction in off-target RNA SNVs to the baseline while maintaining efficient DNA on-target activity. This study reveals a previously overlooked aspect of off-target effects in DNA editing and also demonstrates that such effects can be eliminated by engineering deaminases.
- Publications
-
Off-target RNA mutation induced by DNA base editing and its elimination by mutagenesis
Zhou, C., Sun, Y., Yan, R. et al. Off-target RNA mutation induced by DNA base editing and its elimination by mutagenesis. Nature 571, 275–278 (2019).
(PMID: 31181567) (DOI: 10.1038/s41586-019-1314-0)
Project information
- Experiments
- 2
- Runs
-
1
Run ID Run Name Experiment Sample Data Num Create Date OER044799 OER_Hui_2005121651 OEX001749 OES029699 26 2020-05-12 - Analysis
-
64
Analysis ID Analysis Title Analysis Type Data Date OEZ004417 1116-2.Aligned Reference Alignment 1 2019-03-26 OEZ004418 LP105-3.Aligned Reference Alignment 1 2019-03-26 OEZ004419 ZP-1113-2.Aligned Reference Alignment 1 2019-03-26 OEZ004420 1125-4.Aligned Reference Alignment 1 2019-03-26 OEZ004421 6757-3.Aligned Reference Alignment 1 2019-03-26 OEZ004422 WT-3.Aligned Reference Alignment 1 2019-03-26 OEZ004423 1116-3.Aligned Reference Alignment 1 2019-03-26 OEZ004424 ZP-1114-3.Aligned Reference Alignment 1 2019-03-26 OEZ004425 LP105-1.Aligned Reference Alignment 1 2019-03-26 OEZ004426 1117-1.Aligned Reference Alignment 1 2019-03-26 OEZ004427 ZP-1114-2.Aligned Reference Alignment 1 2019-03-26 OEZ004428 6755-2.Aligned Reference Alignment 1 2019-03-26 OEZ004429 1116-1.Aligned Reference Alignment 1 2019-03-26 OEZ004430 QP115-1.Aligned Reference Alignment 1 2019-03-26 OEZ004431 1125-3.Aligned Reference Alignment 1 2019-03-26 OEZ004432 6755-1.Aligned Reference Alignment 1 2019-03-26 OEZ004433 XXP31-3.Aligned Reference Alignment 1 2019-03-26 OEZ004434 WT-1.Aligned Reference Alignment 1 2019-03-26 OEZ004435 6761-2.Aligned Reference Alignment 1 2019-03-26 OEZ004436 1117-3.Aligned Reference Alignment 1 2019-03-26 OEZ004437 6759-1.Aligned Reference Alignment 1 2019-03-26 OEZ004438 WT-2.Aligned Reference Alignment 1 2019-03-26 OEZ004439 6757-2.Aligned Reference Alignment 1 2019-03-26 OEZ004440 ZP-1112-3.Aligned Reference Alignment 1 2019-03-26 OEZ004441 ZP-1113-1.Aligned Reference Alignment 1 2019-03-26 OEZ004442 LP105-2.Aligned Reference Alignment 1 2019-03-26 OEZ004443 ZP-1115-3.Aligned Reference Alignment 1 2019-03-26 OEZ004444 ZP-1115-1.Aligned Reference Alignment 1 2019-03-26 OEZ004445 6757-1.Aligned Reference Alignment 1 2019-03-26 OEZ004446 XXP31-2.Aligned Reference Alignment 1 2019-03-26 OEZ004447 6761-3.Aligned Reference Alignment 1 2019-03-26 OEZ004448 1117-2.Aligned Reference Alignment 1 2019-03-26 OEZ004449 6761-1.Aligned Reference Alignment 1 2019-03-26 OEZ004450 XXP31-1.Aligned Reference Alignment 1 2019-03-26 OEZ004451 QP115-2.Aligned Reference Alignment 1 2019-03-26 OEZ004452 ZP-1114-1.Aligned Reference Alignment 1 2019-03-26 OEZ004453 ZP-1112-2.Aligned Reference Alignment 1 2019-03-26 OEZ004454 1125-1.Aligned Reference Alignment 1 2019-03-26 OEZ004455 6759-2.Aligned Reference Alignment 1 2019-03-26 OEZ004456 QP115-3.Aligned Reference Alignment 1 2019-03-26 OEZ004457 ZP-1113-3.Aligned Reference Alignment 1 2019-03-26 OEZ004458 ZP-1115-2.Aligned Refernece Alignment 1 2019-03-26 OEZ004660 ZP-1115-2 Reference Alignment 1 2019-06-20 OEZ004661 1116-1 Reference Alignment 1 2019-06-25 OEZ004662 1116-2 Reference Alignment 1 2019-06-26 OEZ004663 1116-3 Reference Alignment 1 2019-06-26 OEZ004664 1117-1 Reference Alignment 1 2019-06-26 OEZ004665 1117-2 Reference Alignment 1 2019-06-27 OEZ004666 1117-3 Reference Alignment 1 2019-06-27 OEZ004667 1123-1 Reference Alignment 1 2019-06-27 OEZ004668 1123-2 Reference Alignment 1 2019-06-27 OEZ004669 1123-3 Reference Alignment 1 2019-06-27 OEZ004676 1149-1 Reference Alignment 1 2019-06-27 OEZ004677 1149-2 Reference Alignment 1 2019-06-27 OEZ004678 1149-3 Reference Alignment 1 2019-06-27 OEZ004685 6759-36-1 Reference Alignment 1 2019-06-27 OEZ004686 6759-36-2 Reference Alignment 1 2019-06-27 OEZ004687 6759-36-3 Reference Alignment 1 2019-06-27 OEZ004699 WT-1 Reference Alignment 1 2019-06-27 OEZ004700 WT-2 Reference Alignment 1 2019-06-27 OEZ004701 WT-3 Reference Alignment 1 2019-06-27 OEZ004714 ZP-1113-1 Reference Alignment 1 2019-06-27 OEZ004715 ZP-1113-2 Reference Alignment 1 2019-06-27 OEZ004716 ZP-1113-3 Reference Alignment 1 2019-06-27
Author Information
- Create Date
- 2019-03-26
- Last Modified
- 2019-08-21
- Submission
- Hui Yang
- Institute of Neuroscience, State Key Laboratory of Neuroscience,