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Efficacy and safety of a clinically relevant foamy vector design in human hematopoietic repopulating cells
Author(s) -
Everson Elizabeth M.,
Hocum Jonah D.,
Trobridge Grant D.
Publication year - 2018
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.3028
Subject(s) - viral vector , virology , biology , haematopoiesis , vector (molecular biology) , stem cell , genetics , recombinant dna , gene
Background Previous studies have shown that foamy viral (FV) vectors are a promising alternative to gammaretroviral and lentiviral vectors and also that insulators can improve FV vector safety. However, in a previous analysis of insulator effects on FV vector safety, strong viral promoters were used to elicit genotoxic events. In the present study, we developed and analyzed the efficacy and safety of a high‐titer, clinically relevant FV vector driven by the housekeeping promoter elongation factor‐1α and insulated with an enhancer blocking A1 insulator (FV‐EGW‐A1). Methods Human CD34 + cord blood cells were exposed to an enhanced green fluorescent protein expressing vector, FV‐EGW‐A1, at a multiplicity of infection of 10 and then maintained in vitro or transplanted into immunodeficient mice. Flow cytometry was used to measure engraftment and marking in vivo . FV vector integration sites were analyzed to assess safety. Results FV‐EGW‐A1 resulted in high‐marking, multilineage engraftment of human repopulating cells with no evidence of silencing. Engraftment was highly polyclonal with no clonal dominance and a promising safety profile based on integration site analysis. Conclusions An FV vector with an elongation factor‐1α promoter and an A1 insulator is a promising vector design for use in the clinic.