443. A Comparison of Fetal Gene Therapy Outcomes in Early and Late Gestation

Abstract

gene marking in the competitive PGK arm reached 60% in both dogs. In contrast, the EF1α arm peaked at 42 days after in vivo gene therapy and never expanded above 10%. The expansion of gene-marked lymphocytes was followed by the appearance of a therapeutic level of CD3+ T cells in both dogs ( Fig 1B). For comparison, this level of lymphocyte gene marking was achieved in only 2 of 5 dogs after 122 and 160 days, respectively, in our previous EF1α-only cohort. The dual-arm dogs exhibit normal peripheral blood cell counts, diverse TCRVΒ rearrangement, and functional response to T cell activating mitogen. These data highlight the utility of the competitive in vivo gene therapy experiments to explore key parameters of vector design and delivery for primary immunodeficiencies and other blood diseases.