Surface-Engineered Lentiviral Vectors for Selective Gene Transfer into Subtypes of Lymphocytes

Lymphocytes have always been among the prime targets in gene therapy, even more so since chimeric antigen receptor (CAR) T cells have reached the clinic. However, other gene therapeutic approaches hold great promise as well. The first part of this review provides an overview of current strategies in...

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Main Authors: Annika M. Frank, Christian J. Buchholz
Format: Article
Language:English
Published: Elsevier 2019-03-01
Series:Molecular Therapy: Methods & Clinical Development
Online Access:http://www.sciencedirect.com/science/article/pii/S2329050118301025
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author Annika M. Frank
Christian J. Buchholz
author_facet Annika M. Frank
Christian J. Buchholz
author_sort Annika M. Frank
collection DOAJ
description Lymphocytes have always been among the prime targets in gene therapy, even more so since chimeric antigen receptor (CAR) T cells have reached the clinic. However, other gene therapeutic approaches hold great promise as well. The first part of this review provides an overview of current strategies in lymphocyte gene therapy. The second part highlights the importance of precise gene delivery into B and T cells as well as distinct subtypes of lymphocytes. This can be achieved with lentiviral vectors (LVs) pseudotyped with engineered glycoproteins recognizing lymphocyte surface markers as entry receptors. Different strategies for envelope glycoprotein engineering and selection of the targeting ligand are discussed. With a CD8-targeted LV that was recently used to achieve proof of principle for the in vivo reprogramming of CAR T cells, these vectors are becoming a key tool to genetically engineer lymphocytes directly in vivo. Keywords: lymphocyte, gene therapy, cancer immunotherapy, entry targeting, lentiviral vector, in vivo gene transfer, CAR T cell
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spelling doaj.art-9d7c29c7e9c9498e98ae537f22b45eb42022-12-21T18:58:25ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012019-03-01121931Surface-Engineered Lentiviral Vectors for Selective Gene Transfer into Subtypes of LymphocytesAnnika M. Frank0Christian J. Buchholz1Division of Medical Biotechnology, Paul-Ehrlich-Institut, 63225 Langen, GermanyDivision of Medical Biotechnology, Paul-Ehrlich-Institut, 63225 Langen, Germany; Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, 63225 Langen, Germany; Corresponding author: Christian J. Buchholz, Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, Paul-Ehrlich Straße 51-59, 63225 Langen, Germany.Lymphocytes have always been among the prime targets in gene therapy, even more so since chimeric antigen receptor (CAR) T cells have reached the clinic. However, other gene therapeutic approaches hold great promise as well. The first part of this review provides an overview of current strategies in lymphocyte gene therapy. The second part highlights the importance of precise gene delivery into B and T cells as well as distinct subtypes of lymphocytes. This can be achieved with lentiviral vectors (LVs) pseudotyped with engineered glycoproteins recognizing lymphocyte surface markers as entry receptors. Different strategies for envelope glycoprotein engineering and selection of the targeting ligand are discussed. With a CD8-targeted LV that was recently used to achieve proof of principle for the in vivo reprogramming of CAR T cells, these vectors are becoming a key tool to genetically engineer lymphocytes directly in vivo. Keywords: lymphocyte, gene therapy, cancer immunotherapy, entry targeting, lentiviral vector, in vivo gene transfer, CAR T cellhttp://www.sciencedirect.com/science/article/pii/S2329050118301025
spellingShingle Annika M. Frank
Christian J. Buchholz
Surface-Engineered Lentiviral Vectors for Selective Gene Transfer into Subtypes of Lymphocytes
Molecular Therapy: Methods & Clinical Development
title Surface-Engineered Lentiviral Vectors for Selective Gene Transfer into Subtypes of Lymphocytes
title_full Surface-Engineered Lentiviral Vectors for Selective Gene Transfer into Subtypes of Lymphocytes
title_fullStr Surface-Engineered Lentiviral Vectors for Selective Gene Transfer into Subtypes of Lymphocytes
title_full_unstemmed Surface-Engineered Lentiviral Vectors for Selective Gene Transfer into Subtypes of Lymphocytes
title_short Surface-Engineered Lentiviral Vectors for Selective Gene Transfer into Subtypes of Lymphocytes
title_sort surface engineered lentiviral vectors for selective gene transfer into subtypes of lymphocytes
url http://www.sciencedirect.com/science/article/pii/S2329050118301025
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