Fig1. Detection of ANGPTL3 expression in liver by RT-PCR.?

Wild type: only one band at 187 bp with primers F1/R1(mAngptl3);?

Homozygous: only one band at 138 bp with primers F2/R2(hANGPTL3);?

Abbr. M, DNA marker; HO, homozygous; HE, heterozygous; WT, wild type.

Fig.2 Detection of mANGPTL3(A) and hANGPTL3(B) expression in serum by ELISA.?

Abbr. HO, homozygous; WT, wild type.

Note. The HO hANGPTL3 mice was 12 weeks old, female.

Fig3. Detection of hANGPTL3 expression in serum in homozygous hANGPTL3 mice by ELISA.?

Abbr. HO, homozygous

Fig.4 Monitoring of serum blood lipids levels in male hANGPTL3 mice (n=3) (In cooperation with the third party).?

Abbr. Hom, homozygous; WT, wild type.

Fig.5 Monitoring of serum blood lipids levels in female hANGPTL3 mice (n=2) (In cooperation with the third party).?

Abbr. Hom, homozygous; WT, wild type.

Fig.6 hANGPT3 mice (male, 8-10 weeks old) were randomly divided into two groups (n=8/group).?Mice were administered with ARO-ANG3, a nucleic acid drug targeting ANGPTL3, synthesized according to the relevant patents. Blood lipids level of hANGPT3 mice before or after dosing were detected.?

Compared to vehicle, ARO-ANG3 treatment group showed a significant decrease in TG, T-CHO and HDL-C. Mean ± SEM. t-test, *P < 0.05, **P < 0.01, ***P < 0.001.

Fig.7 hANGPT3 mice (male, 8-10 weeks old) were randomly divided into two groups (n=8/group). Mice were administered with ARO-ANG3, a nucleic acid drug targeting ANGPTL3, synthesized according to the relevant patents. At day 28 post-dosing, the mice were euthanized, and their livers were collected for the assessment of human ANGPT3 mRNA expression via qPCR.?

The results indicated a significant reduction in human ANGPT3 expression in the ARO-ANG3 treatment group compared to the vehicle control. Mean ± SEM. t-test, ***P < 0.001.

Fig.8 hANGPT3 mice (male, 8-10 weeks old) were randomly divided into two groups(n=8/group).?Mice were administered with ARO-ANG3, a nucleic acid drug targeting ANGPTL3, synthesized according to the relevant patents. Expression level of hANGPT3 before or after dosing at indicated timepoint was detected by ELISA.?

Compared to vehicle, ARO-ANG3 treatment group showed a significant decrease in the expression of hANGPT3. Mean ± SEM. t-test, ***P < 0.001.