Optimizing lentiviral vector transduction of hematopoietic stem cells for gene therapy.

ABSTRACT: Autologous gene therapy using lentiviral vectors (LVs) holds promise for treating monogenetic blood diseases. However, clinical applications can be limited by suboptimal hematopoietic stem cell (HSC) transduction and insufficient quantities of available vector. We recently reported gene therapy for X-linked severe combined immunodeficiency using a protocol in which patient CD34⁺ cells were incubated with two successive transductions. Here we describe an improved protocol for LV delivery to CD34⁺ cells that simplifies product manipulation, reduces vector consumption, and achieves greater vector copy number (VCN) of repopulating HSCs in mouse xenotransplantation assays. Notable findings include the following: (1) the VCN of CD34⁺ cells measured shortly after

SUBMITTER: Jang Y 

PROVIDER: S-EPMC7606410 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature