Evidence map›Paper›PMID 37921437›Full record

ArticleeLife2023

Genomic stability of self-inactivating rabies.

Ernesto Ciabatti, Ana González-Rueda, Daniel de Malmazet, Hassal Lee, Fabio Morgese, Marco Tripodi

Abstract read
In one paragraph

Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. "Self-inactivating" rabies viruses are susceptible to loss of their intended attenuating modification.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  7. Article
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Ernesto CiabattiMRC Laboratory of Molecular Biology, Cambridge, United Kingdom.ORCID 0000-0001-9361-5992
Ana González-RuedaMRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
Daniel de MalmazetMRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
Hassal LeeMRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
Fabio MorgeseMRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
Marco TripodiMRC Laboratory of Molecular Biology, Cambridge, United Kingdom.ORCID 0000-0002-6827-6690

Funding

European Research Council STG-677029Medical Research Council MC_UP_1201/2Medical Research Council MRC-UP_1201/2
6 · The paper itself

Abstract

Transsynaptic viral vectors provide means to gain genetic access to neurons based on synaptic connectivity and are essential tools for the dissection of neural circuit function. Among them, the retrograde monosynaptic ΔG-Rabies has been widely used in neuroscience research. A recently developed engineered version of the ΔG-Rabies, the non-toxic self-inactivating (SiR) virus, allows the long term genetic manipulation of neural circuits. However, the high mutational rate of the rabies virus poses a risk that mutations targeting the key genetic regulatory element in the SiR genome could emerge and revert it to a canonical ΔG-Rabies. Such revertant mutations have recently been identified in a SiR batch. To address the origin, incidence and relevance of these mutations, we investigated the genomic stability of SiR in vitro and in vivo. We found that "revertant" mutations are rare and accumulate only when SiR is extensively amplified in vitro, particularly in suboptimal production cell lines that have insufficient levels of TEV protease activity. Moreover, we confirmed that SiR-CRE, unlike canonical ΔG-Rab-CRE or revertant-SiR-CRE, is non-toxic and that revertant mutations do not emerge in vivo during long-term experiments.

Indexed as

RabiesRabies virusCell LineGenomic InstabilityHumansMutationgeneticsgenomicsmouseneural circuitsneuronal tracingneurosciencerabiesviral vector

Identifiers

PMID37921437
PMCPMC10666929

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.