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Series GSE161632 Query DataSets for GSE161632
Status Public on Dec 31, 2022
Title Cas9 interactions with host RNAs and transposable elements impair neurodevelopment (irCLIP-seq)
Organism Homo sapiens
Experiment type Other
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.
Overall design We first established a hESC line that expressed Cas9 (fused with FLAG) under doxycycline treatment and then performed irCLIP-seq experiments of Cas9. Two replicate Cas9 irCLIP libraries were sequenced.
Contributor(s) Hu Y, Li R, Sun C, Yang M, Yu H, Chen D, Wang J
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Submission date Nov 17, 2020
Last update date Jan 02, 2023
Contact name Denghui Chen
Organization name Sun Yat-sen University
Department Zhongshan School of Medicine
Street address No. 74 Zhongshan 2nd Road
City Guangzhou City
ZIP/Postal code 510080
Country China
Platforms (1)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
Samples (2)
GSM4911572 Cas9 irCLIP-seq replicate 1
GSM4911573 Cas9 irCLIP-seq replicate 2
This SubSeries is part of SuperSeries:
GSE161635 Cas9 interactions with host RNAs and transposable elements impair neurodevelopment
BioProject PRJNA678977
SRA SRP292921

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Supplementary file Size Download File type/resource
GSE161632_RAW.tar 10.8 Mb (http)(custom) TAR (of BED, BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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