Evidence map›Paper›PMID 33270859›Full record

ArticleNucleic acids research2020

HK022 bacteriophage Integrase mediated RMCE as a potential tool for human gene therapy.

Amer Elias, Hala Kassis, Suha Abd Elkader, Natasha Gritsenko, Alessio Nahmad, Hodaya Shir, Liana Younis, Atheer Shannan, Hideki Aihara, Gali Prag and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 39% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
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

12 authors at 2 institutions in 2 countries.

Amer EliasDepartment of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University, Tel-Aviv, Israel.
Hala KassisDepartment of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University, Tel-Aviv, Israel.
Suha Abd ElkaderDepartment of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University, Tel-Aviv, Israel.
Natasha GritsenkoDepartment of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University, Tel-Aviv, Israel.
Alessio NahmadDepartment of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University, Tel-Aviv, Israel.
Hodaya ShirDepartment of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University, Tel-Aviv, Israel.
Liana YounisDepartment of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University, Tel-Aviv, Israel.
Atheer ShannanDepartment of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University, Tel-Aviv, Israel.
Hideki AiharaDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota TwinCities, Minneapolis, MN, 55455, USA.
Gali PragDepartment of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University, Tel-Aviv, Israel.
Ezra YagilDepartment of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University, Tel-Aviv, Israel.
Mikhail KolotDepartment of Biochemistry and Molecular Biology, School of Neurobiology, Biochemistry &Biophysics, Tel-Aviv University, Tel-Aviv, Israel.
Tel Aviv University · ILUniversity of Minnesota · US

Funding

Structural studies of viral replication and invasionR35GM118047 · NIGMS · UNIVERSITY OF MINNESOTA · PI Hideki Aihara · 2016 to 2026
$6.3M
NIGMS NIH HHS R35 GM118047
6 · The paper itself

Abstract

HK022 coliphage site-specific recombinase Integrase (Int) can catalyze integrative site-specific recombination and recombinase-mediated cassette exchange (RMCE) reactions in mammalian cell cultures. Owing to the promiscuity of the 7 bp overlap sequence in its att sites, active 'attB' sites flanking human deleterious mutations were previously identified that may serve as substrates for RMCE reactions for future potential gene therapy. However, the wild type Int proved inefficient in catalyzing such RMCE reactions. To address this low efficiency, variants of Int were constructed and examined by integrative site-specific recombination and RMCE assays in human cells using native 'attB' sites. As a proof of concept, various Int derivatives have demonstrated successful RMCE reactions using a pair of native 'attB' sites that were inserted as a substrate into the human genome. Moreover, successful RMCE reactions were demonstrated in native locations of the human CTNS and DMD genes whose mutations are responsible for Cystinosis and Duchene Muscular Dystrophy diseases, respectively. This work provides a steppingstone for potential downstream therapeutic applications.

Indexed as

Genetic TherapyBacteriophage HK022DNA NucleotidyltransferasesGenome, HumanHumansIntegrasesRecombination, GeneticDNA NucleotidyltransferasesIntegrasesSite-specific recombinase

Identifiers

PMID33270859
PMCPMC7736782
OpenAlexW3110432934

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.