Improved targeting of human CD4+ T cells by nanobody-modified AAV2 gene therapy vectors
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Improved targeting of human CD4+ T cells by nanobody-modified AAV2 gene therapy vectors. / 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.
in: PLOS ONE, Jahrgang 16, Nr. 12, e0261269, 21.12.2021.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Improved targeting of human CD4+ T cells by nanobody-modified AAV2 gene therapy vectors
AU - Hamann, Martin V
AU - Beschorner, Niklas
AU - Vu, Xuan-Khang
AU - Hauber, Ilona
AU - Lange, Ulrike C
AU - Traenkle, Bjoern
AU - Kaiser, Philipp D
AU - Foth, Daniel
AU - Schneider, Carola
AU - Büning, Hildegard
AU - Rothbauer, Ulrich
AU - Hauber, Joachim
PY - 2021/12/21
Y1 - 2021/12/21
N2 - Adeno-associated viruses (AAV) are considered non-pathogenic in humans, and thus have been developed into powerful vector platforms for in vivo 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+ T lymphocytes are largely missing. In fact, a substantial translational bottleneck exists in the field of therapeutic gene transfer that would require in vivo 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+ cells, including primary human peripheral blood mononuclear cells (PBMC) and purified human CD4+ 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+ leukocytes.
AB - Adeno-associated viruses (AAV) are considered non-pathogenic in humans, and thus have been developed into powerful vector platforms for in vivo 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+ T lymphocytes are largely missing. In fact, a substantial translational bottleneck exists in the field of therapeutic gene transfer that would require in vivo 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+ cells, including primary human peripheral blood mononuclear cells (PBMC) and purified human CD4+ 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+ leukocytes.
U2 - 10.1371/journal.pone.0261269
DO - 10.1371/journal.pone.0261269
M3 - SCORING: Journal article
C2 - 34928979
VL - 16
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 12
M1 - e0261269
ER -