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Verfasst von:Bogert, Nicolai [VerfasserIn]   i
 Furkel, Jennifer [VerfasserIn]   i
 Din, Shabana [VerfasserIn]   i
 Braren, I. [VerfasserIn]   i
 Eckstein, Volker [VerfasserIn]   i
 Müller, J. A. [VerfasserIn]   i
 Uhlmann, Lorenz [VerfasserIn]   i
 Katus, Hugo [VerfasserIn]   i
 Konstandin, Mathias [VerfasserIn]   i
Titel:A novel approach to genetic engineering of T-cell subsets by hematopoietic stem cell infection with a bicistronic lentivirus
Verf.angabe:N.V. Bogert, J. Furkel, S. Din, I. Braren, V. Eckstein, J.A. Müller, L. Uhlmann, H.A. Katus & M.H. Konstandin
E-Jahr:2020
Jahr:13 August 2020
Umfang:10 S.
Fussnoten:Gesehen am 12.10.2020
Titel Quelle:Enthalten in: Scientific reports
Ort Quelle:[London] : Springer Nature, 2011
Jahr Quelle:2020
Band/Heft Quelle:10(2020) Artikel-Nummer 13740, 10 Seiten
ISSN Quelle:2045-2322
Abstract:Lentiviral modification of hematopoietic stem cells (HSCs) paved the way for in vivo experimentation and therapeutic approaches in patients with genetic disease. A disadvantage of this method is the use of a ubiquitous promoter leads not only to genetic modification of the leukocyte subset of interest e.g. T-cells, but also all other subsequent leukocyte progeny of the parent HSCs. To overcome this limitation we tested a bicistronic lentivirus, enabling subset specific modifications. Designed novel lentiviral constructs harbor a global promoter (mPGK) regulating mCherry for HSCs selection and a T-cell specific promoter upstream of eGFP. Two T-cell specific promoters were assessed: the distal Lck—(dLck) and the CD3δ-promoter. Transduced HSCs were FACS sorted by mCherry expression and transferred into sublethally irradiated C57/BL6 mice. Successful transplantation and T-cell specific expression of eGFP was monitored by peripheral blood assessment. Furthermore, recruitment response of lentiviral engineered leukocytes to the site of inflammation was tested in a peritonitis model without functional impairment. Our constructed lentivirus enables fast generation of subset specific leukocyte transgenesis as shown in T-cells in vivo and opens new opportunities to modify other HSCs derived subsets in the future.
DOI:doi:10.1038/s41598-020-70793-6
URL:kostenfrei: Volltext: https://doi.org/10.1038/s41598-020-70793-6
 kostenfrei: Volltext: https://www.nature.com/articles/s41598-020-70793-6
 DOI: https://doi.org/10.1038/s41598-020-70793-6
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1735364835
Verknüpfungen:→ Zeitschrift
 
 
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