Evidence map›Paper›PMID 26668323›Full record

ArticleThe Journal of biological chemistry2016

Molecular Determinants of Vectofusin-1 and Its Derivatives for the Enhancement of Lentivirally Mediated Gene Transfer into Hematopoietic Stem/Progenitor Cells.

Saliha Majdoul, Ababacar K Seye, Antoine Kichler, Nathalie Holic, Anne Galy, Burkhard Bechinger, David Fenard

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. 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
2.2field-weighted citation impact, top 11% 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, 33 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

7 authors at 4 institutions in 1 country.

Saliha MajdoulFrom Généthon, 91000 Evry, France, INSERM UMR_S951, 91000 Evry, France, University of Evry, 91000 Evry, France.
Ababacar K SeyeFrom Généthon, 91000 Evry, France, INSERM UMR_S951, 91000 Evry, France.
Antoine KichlerCNRS, UMR_7199, 67401 Illkirch, France, the University of Strasbourg, 67000 Strasbourg, France, and.
Nathalie HolicFrom Généthon, 91000 Evry, France, INSERM UMR_S951, 91000 Evry, France, University of Evry, 91000 Evry, France.
Anne GalyFrom Généthon, 91000 Evry, France, INSERM UMR_S951, 91000 Evry, France, University of Evry, 91000 Evry, France, galy@genethon.fr.
Burkhard Bechingerthe University of Strasbourg, 67000 Strasbourg, France, and the Institut de Chimie, CNRS, UMR_7177, 67401 Strasbourg, France.
David FenardFrom Généthon, 91000 Evry, France, INSERM UMR_S951, 91000 Evry, France, University of Evry, 91000 Evry, France, dfenard@genethon.fr.ORCID http://orcid.org/0000-0003-0242-386X
Centre National de la Recherche Scientifique · FRGenethon (France) · FRUniversité d'Évry Val-d'Essonne · FRInserm · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gene delivery into hCD34+ hematopoietic stem/progenitor cells (HSPCs) using human immunodeficiency virus, type 1-derived lentiviral vectors (LVs) has several promising therapeutic applications. Numerous clinical trials are currently underway. However, the efficiency, safety, and cost of LV gene therapy could be ameliorated by enhancing target cell transduction levels and reducing the amount of LV used on the cells. Several transduction enhancers already exist, such as fibronectin fragments or cationic compounds. Recently, we discovered Vectofusin-1, a new transduction enhancer, also called LAH4-A4, a short histidine-rich amphipathic peptide derived from the LAH4 family of DNA transfection agents. Vectofusin-1 enhances the infectivity of lentiviral and γ-retroviral vectors pseudotyped with various envelope glycoproteins. In this study, we compared a family of Vectofusin-1 isomers and showed that Vectofusin-1 remains the lead peptide for HSPC transduction enhancement with LVs pseudotyped with vesicular stomatitis virus glycoproteins and also with modified gibbon ape leukemia virus glycoproteins. By comparing the capacity of numerous Vectofusin-1 variants to promote the modified gibbon ape leukemia virus glycoprotein-pseudotyped lentiviral vector infectivity of HSPCs, the lysine residues on the N-terminal extremity of Vectofusin-1, a hydrophilic angle of 140° formed by the histidine residues in the Schiffer-Edmundson helical wheel representation, hydrophobic residues consisting of leucine were all found to be essential and helped to define a minimal active sequence. The data also show that the critical determinants necessary for lentiviral transduction enhancement are partially different from those necessary for efficient antibiotic or DNA transfection activity of LAH4 derivatives. In conclusion, these results help to decipher the action mechanism of Vectofusin-1 in the context of hCD34+ cell-based gene therapy.

Indexed as

Genetic VectorsGene Transfer TechniquesLentivirusAmino Acid SequenceAntigens, CD34Antimicrobial Cationic PeptidesDNAGenetic TherapyGlycoproteinsHCT116 CellsHEK293 CellsHeLa CellsHematopoietic Stem CellsHistidineHIV-1HumansAntigens, CD34Antimicrobial Cationic PeptidesDNAGlycoproteinsHistidineLAH(4) protein, syntheticPeptidesgene therapygene transferhematopoietic stem cellslentiviral vectorpeptidesretrovirusVectofusin-1

Identifiers

PMID26668323
PMCPMC4732202
OpenAlexW2209588939

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.