hTTR-V30M(p.V50M)

利用同源重组，将小鼠Ttr 基因进行人源化修饰，包含V30M (p.V50M)突变。

Fig.1 Detection of human TTR (A) and mouse TTR (B) expression in serum by ELISA (male, 7-8wks, n=4). Human TTR was exclusively detectable in the serum from homozygous hTTR-V30M(p.V50M) mice but not in serum from WT C57BL/6 mice. Mouse TTR was exclusively detectable in serum from WT C57BL/6 mice but not in serum from homozygous hTTR-V30M(p.V50M) mice.

Abbr. HO, homozygous; WT, wild type.

Fig.3 Detection of human TTR levels in serum from hTTR-V30M(p.V50M) knock-in mice. Vutrisiran markedly suppressed serum human TTR levels in hTTR-V30M(p.V50M) knock-in mice, maintaining a sustained reduction over a 4-week period. Male, 9-week-old homozygous hTTR-V30M(p.V50M) knock-in mice were treated with PBS or Vutrisiran . Serum was collected at baseline (D0) and on days 7 and 28 post-dosing for hTTR measurement by ELISA. (n=5, Mean±SEM, Unpaired t-test, ****p<0.0001).

Abbr. HO, homozygous.

Fig.4 Detection of human TTR expression in liver, kidney, brain and eye tissues by qPCR. Vutrisiran exclusively suppressed human TTR mRNA expression in liver of hTTR-V30M(p.V50M) knock-in mice. Male, 9-week-old homozygous hTTR-V30M(p.V50M) knock-in mice were treated with PBS or Vutrisiran. Tissues RNA was extracted on days 28 post-dosing, then cDNA libraries were synthesized by reverse transcription, followed by qPCR with human TTR and mouse Gapdh primers. Relative expression represents the human TTR mRNA level relative to its average expression in Group 1 mice. (n=5, Mean±SEM, Unpaired t-test, ns: no significance).