Extended Data Figure 5. In vivo liver-stage efficacy study of BRD7929 in a humanized mouse model.
a, BRD7929 shows single-dose in vivo efficacy in a P. falciparum huHep FRG-knockout mouse liver-stage model. huHep FRG knockout mice were inoculated intravenously with approximately 1 × 105 P. falciparum (NF54HT-GFP-luc) sporozoites and BRD7929 was administered as a single 10 mg kg−1 oral dose 1 day after inoculation (n = 2 for each group, this study was conducted once). Infections were monitored using IVIS. The same colour scale is used for all images. No increase in bioluminescence intensity level was observed from the mice treated with BRD7929 (see Fig. 4b). b, Blood samples were also collected from each mouse 7 days after inoculation (the first day of the blood stage) and analysed for the presence of the blood-stage transcripts PF3D7_0812600 (P. falciparum UCE) using qRT–PCR32 (two biological replicates for each group and three technical replicates for each biological sample). Each dot represents a technical replicate of a sample and each horizontal line represents a mean of technical replicates from each mouse. The presence of the blood-stage parasite specific transcripts was detected from the control (vehicle) mice, while no amplification of the marker was detected after 40 amplification cycles (Ct value = 40) from the mice treated with BRD7929. Primer efficiency and sensitivity of the primer pairs for P. falciparum UCE have a detection limit ranging between 10 and 100 transcript copies33. Approximately 110 µl of combined blood samples from the two treated animals was also cultured in vitro and monitored for an additional 30 days but viable parasites were not detected.