Evidence map›Paper›PMID 26900663›Full record

ArticleNature biotechnology2016

Directed evolution of a recombinase that excises the provirus of most HIV-1 primary isolates with high specificity.

Janet Karpinski, Ilona Hauber, Jan Chemnitz, Carola Schäfer, Maciej Paszkowski-Rogacz, Deboyoti Chakraborty, Niklas Beschorner, Helga Hofmann-Sieber, Ulrike C Lange, Adam Grundhoff and 10 more

Abstract read
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In one paragraph

Article in Nature biotechnology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing 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

71 citing papers in PubMed.

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  16. Precise excision of HTLV-1 provirus with a designer-recombinase.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
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11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Janet KarpinskiMedical Systems Biology, UCC, Medical Faculty Carl Gustav Carus, TU Dresden, Germany.
Ilona HauberHeinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Jan ChemnitzHeinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Carola SchäferHeinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Maciej Paszkowski-RogaczMedical Systems Biology, UCC, Medical Faculty Carl Gustav Carus, TU Dresden, Germany.
Deboyoti ChakrabortyMedical Systems Biology, UCC, Medical Faculty Carl Gustav Carus, TU Dresden, Germany.ORCID http://orcid.org/0000-0002-2300-4333
Niklas BeschornerHeinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Helga Hofmann-SieberHeinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Ulrike C LangeHeinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Adam GrundhoffHeinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Karl HackmannInstitute for Clinical Genetics, University Hospital and Medical Faculty Carl Gustav Carus, TU Dresden, Germany.
Evelin SchrockInstitute for Clinical Genetics, University Hospital and Medical Faculty Carl Gustav Carus, TU Dresden, Germany.
Josephine Abi-GhanemStructural Bioinformatics, BIOTEC TU Dresden, Germany.
M Teresa PisabarroStructural Bioinformatics, BIOTEC TU Dresden, Germany.
Vineeth SurendranathMax Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany.
Axel SchambachInstitute of Experimental Hematology, Hannover Medical School, Hannover, Germany.
Christoph LindnerAgaplesion Diakonieklinikum, Gynecology, Hamburg, Germany.
Jan van LunzenHeinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Joachim HauberHeinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Frank BuchholzMedical Systems Biology, UCC, Medical Faculty Carl Gustav Carus, TU Dresden, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Current combination antiretroviral therapies (cART) efficiently suppress HIV-1 reproduction in humans, but the virus persists as integrated proviral reservoirs in small numbers of cells. To generate an antiviral agent capable of eradicating the provirus from infected cells, we employed 145 cycles of substrate-linked directed evolution to evolve a recombinase (Brec1) that site-specifically recognizes a 34-bp sequence present in the long terminal repeats (LTRs) of the majority of the clinically relevant HIV-1 strains and subtypes. Brec1 efficiently, precisely and safely removes the integrated provirus from infected cells and is efficacious on clinical HIV-1 isolates in vitro and in vivo, including in mice humanized with patient-derived cells. Our data suggest that Brec1 has potential for clinical application as a curative HIV-1 therapy.

Indexed as

AnimalsAntiviral AgentsBase SequenceCells, CulturedDirected Molecular EvolutionHIV-1HIV InfectionsHumansMiceMolecular Sequence DataProvirusesRecombinasesVirus IntegrationAntiviral AgentsRecombinases

Identifiers

PMID26900663

What OpenQuestion holds

Textmetadata
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.