In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 12 ( 2021-12-20), p. e0261269-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0261269
DOI:
10.1371/journal.pone.0261269.g001
DOI:
10.1371/journal.pone.0261269.g002
DOI:
10.1371/journal.pone.0261269.g003
DOI:
10.1371/journal.pone.0261269.g004
DOI:
10.1371/journal.pone.0261269.g005
DOI:
10.1371/journal.pone.0261269.s001
DOI:
10.1371/journal.pone.0261269.s002
DOI:
10.1371/journal.pone.0261269.s003
DOI:
10.1371/journal.pone.0261269.s004
DOI:
10.1371/journal.pone.0261269.s005
DOI:
10.1371/journal.pone.0261269.s006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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