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| Status |
Public on Dec 31, 2022 |
| Title |
Cas9 interactions with host RNAs and transposable elements impair neurodevelopment (RNA-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The CRISPR (clustered regulatory interspaced short palindromic repeats)/ Cas9 (CRISPR-associated protein 9) system-based precise genome editing has revolutionized biomedical studies. As the CRISPR/Cas9 system has been also recently considered to permanently cure genetic diseases via human germline genome editing, a careful risk assessment of this genome engineering tool is required in human early development. Here we perform comprehensive analysis to evaluate the potential impact of Cas9 in human early embryogenesis. We find that even in the absence of synthetic guide RNA, Cas9 can be still guided by endogenous RNAs, and cut the genome of human embryonic cells at low frequency, and the resulting DNA damage induces the intrinsic immune response. Moreover, Cas9 interferes with the spliceosome, and with the suppressor machinery (e.g. L1TD1, APOBEC3G and PIWIL4) of LINE-1 (L1) retrotransposition. Even the transient presence of Cas9 in human embryonic cells induces robust de novo L1 retrotransposition that exacerbates DNA damage, and results in compromised neurodevelopment. Besides the ethical issues, these inevitable and detrimental Cas9-associated impacts on human embryonic development raise such serious safety concerns as to question the clinical use of human germline genome editing.
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| Overall design |
RNA-seq were applied on hESC_WT, hESC_iCas9 and hESC_idCas9 to profile their transcriptomes.
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| Contributor(s) |
Hu Y, Li R, Sun C, Yang M, Yu H, Chen D, Wang J |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Nov 17, 2020 |
| Last update date |
Dec 31, 2022 |
| Contact name |
Denghui Chen |
| E-mail(s) |
chendh39@mail.sysu.edu.cn
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| Organization name |
Sun Yat-sen University
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| Department |
Zhongshan School of Medicine
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| Street address |
No. 74 Zhongshan 2nd Road
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| City |
Guangzhou City |
| ZIP/Postal code |
510080 |
| Country |
China |
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| Platforms (1) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE161635 |
Cas9 interactions with host RNAs and transposable elements impair neurodevelopment |
|
| Relations |
| BioProject |
PRJNA678979 |
| SRA |
SRP292923 |
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