Non-human animals comprising a humanized ASGR1 locus
Non-human animal cells and non-human animals comprising a humanized Asgr1 locus and methods of using such non-human animal cells and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized Asgr1 locus express a human ASGR1 protein or an Asgr1 protein, fragments of which are from human ASGR1. Methods are provided for using such non-human animals comprising a humanized Asgr1 locus to assess in vivo efficacy of human-ASGR1-mediated delivery of therapeutic molecules or therapeutic complexes to the liver and to assess the efficacy of therapeutic molecules or therapeutic complexes acting via human-ASGR1-mediated mechanisms.
1 . A nucleic acid comprising a first nucleic acid sequence that encodes the amino acid sequence as set forth in SEQ ID NO: 3, wherein the nucleic acid further comprises a second nucleic acid sequence selected from the group consisting of the nucleic acid sequence as set forth in SEQ ID NO: 18, the nucleic acid sequence as set forth in SEQ ID NO: 19, the nucleic acid sequence as set forth in SEQ ID NO: 20, and the nucleic acid sequence as set forth in SEQ ID NO:23.
2 . The nucleic acid of claim 1 , comprising the nucleic acid sequence as set forth in SEQ ID NO:24.
3 . The nucleic acid of claim 1 , comprising the nucleic acid sequence as set forth in SEQ ID NO: 21.
4 . A targeting vector comprising the nucleic acid of claim 1 flanked by 5′ and 3′ homology arms corresponding to 5′ and 3′ target sites within an endogenous mouse Asgr1 locus.
5 . A targeting vector comprising the nucleic acid of claim 2 flanked by 5′ and 3′ homology arms corresponding to 5′ and 3′ target sites within an endogenous mouse Asgr1 locus.
6 . A targeting vector comprising the nucleic acid of claim 3 flanked by 5′ and 3′ homology arms corresponding to 5′ and 3′ target sites within an endogenous mouse Asgr1 locus.