Evidence map›Paper›PMID 34549986›Full record

ArticleJournal of virology2021

CRISPR/Cas9 Ablation of Integrated HIV-1 Accumulates Proviral DNA Circles with Reformed Long Terminal Repeats.

Michele Lai, Eyal Maori, Paola Quaranta, Giulia Matteoli, Fabrizio Maggi, Marco Sgarbanti, Stefania Crucitta, Simone Pacini, Ombretta Turriziani, Guido Antonelli and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
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

17 citing papers in PubMed, 24 citations in OpenAlex.

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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

13 authors at 3 institutions in 2 countries.

Michele LaiRetrovirus Center, Virology Section, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisagrid.5395.a, Pisa, Italy.ORCID 0000-0001-7597-123X
Eyal MaoriLaboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridgegrid.5335.0, Cambridge, United Kingdom.
Paola QuarantaRetrovirus Center, Virology Section, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisagrid.5395.a, Pisa, Italy.
Giulia MatteoliRetrovirus Center, Virology Section, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisagrid.5395.a, Pisa, Italy.
Fabrizio MaggiDepartment of Medicine and Surgery, University of Insubria, Varese, Italy.
Marco SgarbantiNational Institute of Health, Rome, Italy.ORCID 0000-0002-0433-5110
Stefania CrucittaPharmacology Unit, Department of Clinical and Experimental Medicine, University of Pisagrid.5395.a, Pisa, Italy.
Simone PaciniHematology Unit, Department of Clinical and Experimental Medicine, University of Pisagrid.5395.a, Pisa, Italy.
Ombretta TurrizianiLaboratory of Virology, Department of Molecular Medicine, Sapienza University of Romegrid.7841.a, Rome, Italy.ORCID 0000-0001-6400-9168
Guido AntonelliLaboratory of Virology, Department of Molecular Medicine, Sapienza University of Romegrid.7841.a, Rome, Italy.
Jonathan L HeeneyLaboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridgegrid.5335.0, Cambridge, United Kingdom.
Giulia FreerRetrovirus Center, Virology Section, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisagrid.5395.a, Pisa, Italy.
Mauro PistelloRetrovirus Center, Virology Section, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisagrid.5395.a, Pisa, Italy.ORCID 0000-0003-0908-6253
University of Pisa · ITIstituto Pasteur · ITUniversity of Cambridge · GB

Funding

EC | H2020 | H2020 Priority Excellent Science | H2020 Future and Emerging Technologies (FET) 862714Ministero Università e Ricerca, PRIN 2017 2017KM79NNRegione Toscana (Tuscany Region) SENSOR
6 · The paper itself

Abstract

Gene editing may be used to excise the human immunodeficiency virus type 1 (HIV-1) provirus from the host cell genome, possibly eradicating the infection. Here, using cells acutely or latently infected by HIV-1 and treated with long terminal repeat (LTR)-targeting CRISPR/Cas9, we show that the excised HIV-1 provirus persists for a few weeks and may rearrange in circular molecules. Although circular proviral DNA is naturally formed during HIV-1 replication, we observed that gene editing might increase proviral DNA circles with restored LTRs. These extrachromosomal elements were recovered and probed for residual activity through their transfection in uninfected cells. We discovered that they can be transcriptionally active in the presence of Tat and Rev. Although confirming that gene editing is a powerful tool to eradicate HIV-1 infection, this work highlights that, to achieve this goal, the LTRs must be cleaved in several pieces to avoid residual activity and minimize the risk of reintegration in the context of genomic instability, possibly caused by the off-target activity of Cas9.

Indexed as

CRISPR-Cas SystemsDNA, CircularTerminal Repeat SequencesCRISPR-Associated Protein 9Gene EditingGene Expression Regulation, ViralGenetic TherapyHEK293 CellsHIV-1HIV InfectionsHumansProvirusesRNA, Guide, CRISPR-Cas SystemsCRISPR-Associated Protein 9DNA, CircularRNA, Guide, CRISPR-Cas SystemsCRISPR/Cas9endonucleaseendonucleasesgene editinggene therapyHIV-1J-Latlatent infectionlatent reservoirRevTat

Identifiers

PMID34549986
PMCPMC8577360
OpenAlexW3200977854

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.