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Springer Nature [academic journals on nature.com], Gene Therapy, 12(19), p. 1133-1140, 2012

DOI: 10.1038/gt.2011.206

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Development of the Nanobody display technology to target lentiviral vectors to antigen-presenting cells

Journal article published in 2012 by Cleo Goyvaerts, Kurt De Groeve, Jozef Dingemans, Sandra Van Lint, Lander Robays, Carlo Heirman, J. Reiser, X.-Y. Zhang, Kris Thielemans, Patrick De Baetselier, Geert Raes ORCID, Karine Breckpot ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Lentiviral vectors (LVs) provide unique opportunities for the development of immunotherapeutic strategies, as they transduce a variety of cells in situ, including antigen-presenting cells (APCs). Engineering LVs to specifically transduce APCs is required to promote their translation towards the clinic. We report on the Nanobody (Nb) display technology to target LVs to dendritic cells (DCs) and macrophages. This innovative approach exploits the budding mechanism of LVs to incorporate an APC-specific Nb and a binding-defective, fusion-competent form of VSV.G in the viral envelope. In addition to production of high titer LVs, we demonstrated selective, Nb-dependent transduction of mouse DCs and macrophages both in vitro and in situ. Moreover, this strategy was translated to a human model in which selective transduction of in vitro generated or lymph node (LN)-derived DCs and macrophages, was demonstrated. In conclusion, the Nb display technology is an attractive approach to generate LVs targeted to specific cell types.Gene Therapy advance online publication, 12 January 2012; doi:10.1038/gt.2011.206.