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Transcriptome Engineering with RNA-Targeting Type VI-D CRISPR Effectors
Konermann S, Lotfy P, Brideau NJ, Oki J, Shokhirev MN, Hsu PD.. Cell, 2018-03-15
Topic: Brain proteins, microglia and lab models
Class 2 CRISPR-Cas systems endow microbes with diverse mechanisms for adaptive immunity. Here, we analyzed prokaryotic genome and metagenome sequences to identify an uncharacterized family of RNA-guided, RNA-targeting CRISPR systems that we classify as type VI-D. Biochemical characterization and protein engineering of seven distinct orthologs generated a ribonuclease effector derived from Ruminococcus flavefaciens XPD3002 (CasRx) with robust activity in human cells. CasRx-mediated knockdown exhibits high efficiency and specificity relative to RNA interference across diverse endogenous transcripts. As one of the most compact single-effector Cas enzymes, CasRx can also be flexibly packaged into adeno-associated virus. We target virally encoded, catalytically inactive CasRx to cis elements of pre-mRNA to manipulate alternative splicing, alleviating dysregulated tau isoform ratios in a neuronal model of frontotemporal dementia. Our results present CasRx as a programmable RNA-binding module for efficient targeting of cellular RNA, enabling a general platform for transcriptome engineering and future therapeutic development.
Key findings
- Our results present CasRx as a programmable RNA-binding module for efficient targeting of cellular RNA, enabling a general platform for transcriptome engineering and future therapeutic development.
Why it matters
The RNA-targeting CRISPR effector CasRx was engineered to work in human cells and was used to manipulate alternative splicing, alleviating dysregulated tau isoform ratios in a neuronal model of frontotemporal dementia. This is early laboratory work toward a possible platform for future therapeutic development, not a treatment tested in patients.
Study details
- Evidence strengthLow
How this study scored 51/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell) |
| Journal's citation record | 4 / 4 | Cell: journal h-index 1,220 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 7 / 7 | Cited 1,161 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 116.1 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 5 / 6 | Cited 32.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 4 / 4 | Cited 430 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Patrick D. Hsu: h-index 37 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Salk Institute for Biological Studies: institution h-index 1,011 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29551272) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 51 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Konermann, S., Lotfy, P., Brideau, N. J., Oki, J., Shokhirev, M. N., & Hsu, P. D. (2018). Transcriptome Engineering with RNA-Targeting Type VI-D CRISPR Effectors. Cell. https://doi.org/10.1016/j.cell.2018.02.033
Vancouver
Konermann S, Lotfy P, Brideau NJ, Oki J, Shokhirev MN, Hsu PD. Transcriptome Engineering with RNA-Targeting Type VI-D CRISPR Effectors. Cell. 2018. doi:10.1016/j.cell.2018.02.033. PMID: 29551272.
BibTeX
@article{konermann2018-29551272,
author = {Konermann, S. and Lotfy, P. and Brideau, N. J. and Oki, J. and Shokhirev, M. N. and Hsu, P. D.},
title = {{Transcriptome Engineering with RNA-Targeting Type VI-D CRISPR Effectors}},
journal = {Cell},
year = {2018},
doi = {10.1016/j.cell.2018.02.033},
pmid = {29551272},
url = {https://doi.org/10.1016/j.cell.2018.02.033}
}
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