Figure 4.

Mechanisms detracting from the infused vector dose and potential solutions

(A) Several mechanisms can detract from the administered vector dose, reducing the effective on-target dose (shown as darker pink fraction). Among them are the antibody-mediated incapacitation of particles, their uptake by phagocytes and off-target transduction. (B) Antibody-mediated immune responses against vector particles can be reduced by cleaving serum IgG before vector administration using IgG-degrading enzyme from Streptococcus pyogenes (IdeS). (C) LVs can be shielded against phagocytosis by incorporating CD47 into the LV envelope during production (left). CD47 engages signal-regulatory protein alpha (SIRPα) when LV particles (red dots) encounter myeloid cells. Through interaction of CD47 and SIRPα, phagocytosis is inhibited.