A lentiviral vector B cell gene therapy platform for the delivery of the anti-HIV-1 eCD4-Ig-knob-in-hole-reversed immunoadhesin

• DOI: 10.1016/j.omtm.2023.02.004
• Publication Date: 2023-02-11T02:35:54Z
• Authors: Eirini Vamva; Stosh Ozog; Daniel P. Leaman; Rene Yu-Hong Cheng; Nicholas J. Irons; Andee Ott; Claire Stoffers; Iram Khan; Geraldine K.E. Go...; Matthew R. Gardner; Michael Farzan; David J. Rawlings; Michael B. Zwick; Richard G. James; Bruce E. Torbett
• Keywords: Transduction (biophysics)

Barriers to effective gene therapy for many diseases include the number of modified target cells required achieve therapeutic outcomes and host immune responses expressed proteins. As long-lived specialized protein secretion, antibody-secreting B are an attractive foreign expression in blood tissue. To neutralize HIV-1, we developed a lentiviral vector (LV) platform delivery anti-HIV-1 immunoadhesin, eCD4-Ig, cells. The EμB29 enhancer/promoter LV limited non-B cell lineages. By engineering knob-in-hole-reversed (KiHR) modification CH3-Fc eCD4-Ig domain, reduced interactions between endogenous immunoglobulin G proteins, which improved HIV-1 neutralization potency. Unlike previous approaches non-lymphoid cells, eCD4-Ig-KiHR produced promoted neutralizing protection without requiring exogenous TPST2, tyrosine sulfation enzyme function. This finding indicated that machinery is well suited produce Lastly, overcome inefficient transduction efficiency associated with VSV-G primary optimized measles pseudotyped packaging methodology achieved up 75% efficiency. Overall, our findings support utility platforms delivery.