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Mol Ther Methods Clin Dev. 2018 Oct 17;12:19-31. doi: 10.1016/j.omtm.2018.10.006. eCollection 2019 Mar 15.

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

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Division of Medical Biotechnology, Paul-Ehrlich-Institut, 63225 Langen, Germany.
Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, 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.


CAR T cell; cancer immunotherapy; entry targeting; gene therapy; in vivo gene transfer; lentiviral vector; lymphocyte

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