Adapter-Mediated Transduction with Lentiviral Vectors: A Novel Tool for Cell-Type-Specific Gene Transfer

Cordes, Nicole; Winter, Nora; Kolbe, Carolin; Kotter, Bettina; Mittelstaet, Joerg; Assenmacher, Mario; Cathomen, Toni; Kaiser, Andrew; Schaser, Thomas

doi:10.3390/v14102157

Open AccessArticle

Adapter-Mediated Transduction with Lentiviral Vectors: A Novel Tool for Cell-Type-Specific Gene Transfer

by

Nicole Cordes

^1,†,

Nora Winter

^1,†

,

Carolin Kolbe

¹,

Bettina Kotter

¹,

Joerg Mittelstaet

¹,

Mario Assenmacher

¹,

Toni Cathomen

^2,3

,

Andrew Kaiser

¹ and

Thomas Schaser

^1,*

¹

Miltenyi Biotec B.V. & Co. KG, 51429 Bergisch Gladbach, Germany

²

Institute for Transfusion Medicine and Gene Therapy, Medical Center-University of Freiburg, 79106 Freiburg, Germany

³

Center for chronic Immunodeficiency, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Viruses 2022, 14(10), 2157; https://doi.org/10.3390/v14102157

Submission received: 31 August 2022 / Revised: 21 September 2022 / Accepted: 26 September 2022 / Published: 30 September 2022

(This article belongs to the Special Issue Structure and Cell Biology of Viral Infection)

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Abstract

Selective gene delivery to a cell type of interest utilizing targeted lentiviral vectors (LVs) is an efficient and safe strategy for cell and gene therapy applications, including chimeric antigen receptor (CAR)-T cell therapy. LVs pseudotyped with measles virus envelope proteins (MV-LVs) have been retargeted by ablating binding to natural receptors while fusing to a single-chain antibody specific for the antigen of choice. However, the broad application of MV-LVs is hampered by the laborious LV engineering required for every new target. Here, we report the first versatile targeting system for MV-LVs that solely requires mixing with biotinylated adapter molecules to enable selective gene transfer. The analysis of the selectivity in mixed cell populations revealed transduction efficiencies below the detection limit in the absence of an adapter and up to 5000-fold on-to-off-target ratios. Flexibility was confirmed by transducing cell lines and primary cells applying seven different adapter specificities in total. Furthermore, adapter mixtures were applied to generate CAR-T cells with varying CD4/CD8-ratios in a single transduction step. In summary, a selective and flexible targeting system was established that may serve to improve the safety and efficacy of cellular therapies. Compatibility with a wide range of readily available biotinylated molecules provides an ideal technology for a variety of applications.

Keywords: lentiviral vectors; gene therapy; CAR-T cells; immunotherapy

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MDPI and ACS Style

Cordes, N.; Winter, N.; Kolbe, C.; Kotter, B.; Mittelstaet, J.; Assenmacher, M.; Cathomen, T.; Kaiser, A.; Schaser, T. Adapter-Mediated Transduction with Lentiviral Vectors: A Novel Tool for Cell-Type-Specific Gene Transfer. Viruses 2022, 14, 2157. https://doi.org/10.3390/v14102157

AMA Style

Cordes N, Winter N, Kolbe C, Kotter B, Mittelstaet J, Assenmacher M, Cathomen T, Kaiser A, Schaser T. Adapter-Mediated Transduction with Lentiviral Vectors: A Novel Tool for Cell-Type-Specific Gene Transfer. Viruses. 2022; 14(10):2157. https://doi.org/10.3390/v14102157

Chicago/Turabian Style

Cordes, Nicole, Nora Winter, Carolin Kolbe, Bettina Kotter, Joerg Mittelstaet, Mario Assenmacher, Toni Cathomen, Andrew Kaiser, and Thomas Schaser. 2022. "Adapter-Mediated Transduction with Lentiviral Vectors: A Novel Tool for Cell-Type-Specific Gene Transfer" Viruses 14, no. 10: 2157. https://doi.org/10.3390/v14102157

APA Style

Cordes, N., Winter, N., Kolbe, C., Kotter, B., Mittelstaet, J., Assenmacher, M., Cathomen, T., Kaiser, A., & Schaser, T. (2022). Adapter-Mediated Transduction with Lentiviral Vectors: A Novel Tool for Cell-Type-Specific Gene Transfer. Viruses, 14(10), 2157. https://doi.org/10.3390/v14102157

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Adapter-Mediated Transduction with Lentiviral Vectors: A Novel Tool for Cell-Type-Specific Gene Transfer

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