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. 2019 Mar 7;27(4):866–877. doi: 10.1016/j.ymthe.2019.03.003

Figure 5.

Figure 5

Repeat Administration of ZFN mRNA-LNP with Single AAV Donor Delivery for Increasing Targeted Integration of Therapeutic Transgene In Vivo

(A) Liver genome-editing results of repeat dosing (14-day intervals, 2 mg/kg) of LNP containing 48641/31523 ZFN mRNAs into mice. The first dosing also included co-delivery of 1.5e12 vector genomes (vg) AAV8 encoding a human IDS transgene donor with homology arms flanking the ZFN cut site in the ALB gene and a splice acceptor just upstream of the transgene coding region. (n = 3 per group) (p = 0.011 comparing doses 1 and 3). (B) IDS activity in plasma that was collected from the mice described in (A) (n = 3 per group) (p = 0.023 comparing doses 1 and 3). (C) Liver genome-editing results of repeat dosing (7-day intervals, 2 mg/kg) of LNP containing 48641/31523 ZFN mRNAs into mice. The first dosing also included co-delivery of 1.5e12 vector genomes (vg) AAV8 encoding the same human IDS transgene donor described in (A) (n = 3–4 per group) (p = 0.0017 comparing doses 1 and 2). (D) IDS activity in plasma that was collected from the mice described in (C) (n = 3-4 per group) (p = 0.013 comparing doses 1 and 2).