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Medientyp:
E-Artikel
Titel:
Improved targeting of human CD4+ T cells by nanobody-modified AAV2 gene therapy vectors
Beteiligte:
Hamann, Martin V.;
Beschorner, Niklas;
Vu, Xuan-Khang;
Hauber, Ilona;
Lange, Ulrike C.;
Traenkle, Bjoern;
Kaiser, Philipp D.;
Foth, Daniel;
Schneider, Carola;
Büning, Hildegard;
Rothbauer, Ulrich;
Hauber, Joachim
Erschienen:
Public Library of Science (PLoS), 2021
Erschienen in:PLOS ONE
Sprache:
Englisch
DOI:
10.1371/journal.pone.0261269
ISSN:
1932-6203
Entstehung:
Anmerkungen:
Beschreibung:
<jats:p>Adeno-associated viruses (AAV) are considered non-pathogenic in humans, and thus have been developed into powerful vector platforms for<jats:italic>in vivo</jats:italic>gene therapy. Although the various AAV serotypes display broad tropism, frequently infecting multiple tissues and cell types, vectors for specific and efficient targeting of human CD4<jats:sup>+</jats:sup>T lymphocytes are largely missing. In fact, a substantial translational bottleneck exists in the field of therapeutic gene transfer that would require<jats:italic>in vivo</jats:italic>delivery into peripheral disease-related lymphocytes for subsequent genome editing. To solve this issue, capsid modification for retargeting AAV tropism, and in turn improving vector potency, is considered a promising strategy. Here, we genetically modified the minor AAV2 capsid proteins, VP1 and VP2, with a set of novel nanobodies with high-affinity for the human CD4 receptor. These novel vector variants demonstrated improved targeting of human CD4<jats:sup>+</jats:sup>cells, including primary human peripheral blood mononuclear cells (PBMC) and purified human CD4<jats:sup>+</jats:sup>T lymphocytes. Thus, the technical approach presented here provides a promising strategy for developing specific gene therapy vectors, particularly targeting disease-related peripheral blood CD4<jats:sup>+</jats:sup>leukocytes.</jats:p>