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Comprehensive off-target analysis of dCas9-SAM-mediated HIV reactivation via long noncoding RNA and mRNA profiling

Overview of attention for article published in BMC Medical Genomics, September 2018
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (54th percentile)
  • Good Attention Score compared to outputs of the same age and source (70th percentile)

Mentioned by

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6 tweeters

Citations

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8 Dimensions

Readers on

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34 Mendeley
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Title
Comprehensive off-target analysis of dCas9-SAM-mediated HIV reactivation via long noncoding RNA and mRNA profiling
Published in
BMC Medical Genomics, September 2018
DOI 10.1186/s12920-018-0394-2
Pubmed ID
Authors

Yonggang Zhang, Gustavo Arango, Fang Li, Xiao, Raj Putatunda, Jun Yu, Xiao-Feng Yang, Hong Wang, Layne T. Watson, Liqing Zhang, Wenhui Hu

Abstract

CRISPR/CAS9 (epi)genome editing revolutionized the field of gene and cell therapy. Our previous study demonstrated that a rapid and robust reactivation of the HIV latent reservoir by a catalytically-deficient Cas9 (dCas9)-synergistic activation mediator (SAM) via HIV long terminal repeat (LTR)-specific MS2-mediated single guide RNAs (msgRNAs) directly induces cellular suicide without additional immunotherapy. However, potential off-target effect remains a concern for any clinical application of Cas9 genome editing and dCas9 epigenome editing. After dCas9 treatment, potential off-target responses have been analyzed through different strategies such as mRNA sequence analysis, and functional screening. In this study, a comprehensive analysis of the host transcriptome including mRNA, lncRNA, and alternative splicing was performed using human cell lines expressing dCas9-SAM and HIV-targeting msgRNAs. The control scrambled msgRNA (LTR_Zero), and two LTR-specific msgRNAs (LTR_L and LTR_O) groups show very similar expression profiles of the whole transcriptome. Among 839 identified lncRNAs, none exhibited significantly different expression in LTR_L vs. LTR_Zero group. In LTR_O group, only TERC and scaRNA2 lncRNAs were significantly decreased. Among 142,791 mRNAs, four genes were differentially expressed in LTR_L vs. LTR_Zero group. There were 21 genes significantly downregulated in LTR_O vs. either LTR_Zero or LTR_L group and one third of them are histone related. The distributions of different types of alternative splicing were very similar either within or between groups. There were no apparent changes in all the lncRNA and mRNA transcripts between the LTR_L and LTR_Zero groups. This is an extremely comprehensive study demonstrating the rare off-target effects of the HIV-specific dCas9-SAM system in human cells. This finding is encouraging for the safe application of dCas9-SAM technology to induce target-specific reactivation of latent HIV for an effective "shock-and-kill" strategy.

Twitter Demographics

The data shown below were collected from the profiles of 6 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 34 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 26%
Student > Bachelor 5 15%
Researcher 4 12%
Other 3 9%
Student > Master 3 9%
Other 3 9%
Unknown 7 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 21%
Agricultural and Biological Sciences 6 18%
Medicine and Dentistry 3 9%
Neuroscience 2 6%
Nursing and Health Professions 2 6%
Other 6 18%
Unknown 8 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 August 2019.
All research outputs
#8,398,146
of 15,561,549 outputs
Outputs from BMC Medical Genomics
#350
of 812 outputs
Outputs of similar age
#123,261
of 274,982 outputs
Outputs of similar age from BMC Medical Genomics
#3
of 10 outputs
Altmetric has tracked 15,561,549 research outputs across all sources so far. This one is in the 45th percentile – i.e., 45% of other outputs scored the same or lower than it.
So far Altmetric has tracked 812 research outputs from this source. They receive a mean Attention Score of 4.7. This one has gotten more attention than average, scoring higher than 55% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 274,982 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.
We're also able to compare this research output to 10 others from the same source and published within six weeks on either side of this one. This one has scored higher than 7 of them.