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A Biosafety Study of Human Umbilical Cord Blood Mononuclear Cells Transduced with Adenoviral Vector Carrying Human Vascular Endothelial Growth Factor cDNA In Vitro

The biosafety of gene therapy remains a crucial issue for both the direct and cell-mediated delivery of recombinant cDNA encoding biologically active molecules for the pathogenetic correction of congenital or acquired disorders. The diversity of vector systems and cell carriers for the delivery of t...

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Autores principales: Salafutdinov, Ilnur I., Gatina, Dilara Z., Markelova, Maria I., Garanina, Ekaterina E., Malanin, Sergey Yu., Gazizov, Ilnaz M., Izmailov, Andrei A., Rizvanov, Albert A., Islamov, Rustem R., Palotás, András, Safiullov, Zufar Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377014/
https://www.ncbi.nlm.nih.gov/pubmed/37509661
http://dx.doi.org/10.3390/biomedicines11072020
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author Salafutdinov, Ilnur I.
Gatina, Dilara Z.
Markelova, Maria I.
Garanina, Ekaterina E.
Malanin, Sergey Yu.
Gazizov, Ilnaz M.
Izmailov, Andrei A.
Rizvanov, Albert A.
Islamov, Rustem R.
Palotás, András
Safiullov, Zufar Z.
author_facet Salafutdinov, Ilnur I.
Gatina, Dilara Z.
Markelova, Maria I.
Garanina, Ekaterina E.
Malanin, Sergey Yu.
Gazizov, Ilnaz M.
Izmailov, Andrei A.
Rizvanov, Albert A.
Islamov, Rustem R.
Palotás, András
Safiullov, Zufar Z.
author_sort Salafutdinov, Ilnur I.
collection PubMed
description The biosafety of gene therapy remains a crucial issue for both the direct and cell-mediated delivery of recombinant cDNA encoding biologically active molecules for the pathogenetic correction of congenital or acquired disorders. The diversity of vector systems and cell carriers for the delivery of therapeutic genes revealed the difficulty of developing and implementing a safe and effective drug containing artificial genetic material for the treatment of human diseases in practical medicine. Therefore, in this study we assessed changes in the transcriptome and secretome of umbilical cord blood mononuclear cells (UCB-MCs) genetically modified using adenoviral vector (Ad5) carrying cDNA encoding human vascular endothelial growth factor (VEGF165) or reporter green fluorescent protein (GFP). A preliminary analysis of UCB-MCs transduced with Ad5-VEGF165 and Ad5-GFP with MOI of 10 showed efficient transgene expression in gene-modified UCB-MCs at mRNA and protein levels. The whole transcriptome sequencing of native UCB-MCs, UCB-MC+Ad5-VEGF165, and UCB-MC+Ad5-GFP demonstrated individual sample variability rather than the effect of Ad5 or the expression of recombinant vegf165 on UCB-MC transcriptomes. A multiplex secretome analysis indicated that neither the transduction of UCB-MCs with Ad5-GFP nor with Ad5-VEGF165 affects the secretion of the studied cytokines, chemokines, and growth factors by gene-modified cells. Here, we show that UCB-MCs transduced with Ad5 carrying cDNA encoding human VEGF165 efficiently express transgenes and preserve transcriptome and secretome patterns. This data demonstrates the biosafety of using UCB-MCs as cell carriers of therapeutic genes.
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spelling pubmed-103770142023-07-29 A Biosafety Study of Human Umbilical Cord Blood Mononuclear Cells Transduced with Adenoviral Vector Carrying Human Vascular Endothelial Growth Factor cDNA In Vitro Salafutdinov, Ilnur I. Gatina, Dilara Z. Markelova, Maria I. Garanina, Ekaterina E. Malanin, Sergey Yu. Gazizov, Ilnaz M. Izmailov, Andrei A. Rizvanov, Albert A. Islamov, Rustem R. Palotás, András Safiullov, Zufar Z. Biomedicines Article The biosafety of gene therapy remains a crucial issue for both the direct and cell-mediated delivery of recombinant cDNA encoding biologically active molecules for the pathogenetic correction of congenital or acquired disorders. The diversity of vector systems and cell carriers for the delivery of therapeutic genes revealed the difficulty of developing and implementing a safe and effective drug containing artificial genetic material for the treatment of human diseases in practical medicine. Therefore, in this study we assessed changes in the transcriptome and secretome of umbilical cord blood mononuclear cells (UCB-MCs) genetically modified using adenoviral vector (Ad5) carrying cDNA encoding human vascular endothelial growth factor (VEGF165) or reporter green fluorescent protein (GFP). A preliminary analysis of UCB-MCs transduced with Ad5-VEGF165 and Ad5-GFP with MOI of 10 showed efficient transgene expression in gene-modified UCB-MCs at mRNA and protein levels. The whole transcriptome sequencing of native UCB-MCs, UCB-MC+Ad5-VEGF165, and UCB-MC+Ad5-GFP demonstrated individual sample variability rather than the effect of Ad5 or the expression of recombinant vegf165 on UCB-MC transcriptomes. A multiplex secretome analysis indicated that neither the transduction of UCB-MCs with Ad5-GFP nor with Ad5-VEGF165 affects the secretion of the studied cytokines, chemokines, and growth factors by gene-modified cells. Here, we show that UCB-MCs transduced with Ad5 carrying cDNA encoding human VEGF165 efficiently express transgenes and preserve transcriptome and secretome patterns. This data demonstrates the biosafety of using UCB-MCs as cell carriers of therapeutic genes. MDPI 2023-07-18 /pmc/articles/PMC10377014/ /pubmed/37509661 http://dx.doi.org/10.3390/biomedicines11072020 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Salafutdinov, Ilnur I.
Gatina, Dilara Z.
Markelova, Maria I.
Garanina, Ekaterina E.
Malanin, Sergey Yu.
Gazizov, Ilnaz M.
Izmailov, Andrei A.
Rizvanov, Albert A.
Islamov, Rustem R.
Palotás, András
Safiullov, Zufar Z.
A Biosafety Study of Human Umbilical Cord Blood Mononuclear Cells Transduced with Adenoviral Vector Carrying Human Vascular Endothelial Growth Factor cDNA In Vitro
title A Biosafety Study of Human Umbilical Cord Blood Mononuclear Cells Transduced with Adenoviral Vector Carrying Human Vascular Endothelial Growth Factor cDNA In Vitro
title_full A Biosafety Study of Human Umbilical Cord Blood Mononuclear Cells Transduced with Adenoviral Vector Carrying Human Vascular Endothelial Growth Factor cDNA In Vitro
title_fullStr A Biosafety Study of Human Umbilical Cord Blood Mononuclear Cells Transduced with Adenoviral Vector Carrying Human Vascular Endothelial Growth Factor cDNA In Vitro
title_full_unstemmed A Biosafety Study of Human Umbilical Cord Blood Mononuclear Cells Transduced with Adenoviral Vector Carrying Human Vascular Endothelial Growth Factor cDNA In Vitro
title_short A Biosafety Study of Human Umbilical Cord Blood Mononuclear Cells Transduced with Adenoviral Vector Carrying Human Vascular Endothelial Growth Factor cDNA In Vitro
title_sort biosafety study of human umbilical cord blood mononuclear cells transduced with adenoviral vector carrying human vascular endothelial growth factor cdna in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377014/
https://www.ncbi.nlm.nih.gov/pubmed/37509661
http://dx.doi.org/10.3390/biomedicines11072020
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