A - Human Necessities – 01 – K
Patent
A - Human Necessities
01
K
A01K 67/027 (2006.01) A01K 67/033 (2006.01) A01N 63/00 (2006.01) A61K 39/00 (2006.01) C12N 5/06 (2006.01) C12N 9/12 (2006.01) C12N 9/72 (2006.01) C12N 15/00 (2006.01) C12N 15/09 (2006.01) C12N 15/11 (2006.01) C12N 15/63 (2006.01) A61K 35/12 (2006.01) A01N 65/00 (2006.01)
Patent
CA 2389646
The present invention relates to the preparation of non-human animals having chimeric livers, whereby some or substantially all of the hepatocytes present are human hepatocytes. It is based, at least in part, on the discovery that rats, tolerized in utero against human hepatocytes, were found to serve as long-term hosts for human hepatocytes introduced post-natally, and the introduced hepatocytes maintained their differentiated phenotype, as evidenced by continued production of human albumin. The present invention further relates to the use of such animals as models of various liver diseases, including viral invention. Such embodiments are based on the discovery that transplanted human hepatocytes in chemeric livers were found to be susceptible to HBV infection in situ and supported replication of the virus as evidenced by the appearance of HBsAg in serum and in liver cells and by the presence of covalently closed circular DNA forms in liver.
La présente invention porte sur la préparation d'animaux possédant des foies chimères, certains ou la majorité des hépatocytes présents étant des hépatocytes humains. Cette invention est basée, au moins partiellement, sur la découverte que des rats, tolérésin utero par rapport aux hépatocytes, se sont avérés servir d'hôtes à long terme pour des hépatocytes humains introduits après la naissance, les hépatocytes humains introduits ayant conservé leur phénotype différentiel, tel que le met en évidence la production continue d'albumine humaine. La présente invention porte sur l'utilisation de ces animaux comme modèles de diverses pathologies du foie, y compris l'invention virale. Ces réalisations sont basées sur la découverte que des hépatocytes humains transplantés dans des foies chimères se sont avérés être sensibles à l'infection par HBV in situ et à la réplication soutenue du virus tel que le met en évidence l'apparence de HBsAg dans le sérum et dans les cellules du foie et la présence dans le foie de formes d'ADN circulaires, fermées de manière covalente.
Wu Catherine H.
Wu George Y.
Smart & Biggar
The University Of Connecticut
LandOfFree
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