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Viral gene transfer for xenotransplantation
Author(s) -
Pfeifer A.
Publication year - 2010
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.2010.00573_11.x
Subject(s) - xenotransplantation , transgenesis , biology , rna interference , transgene , gene , retrovirus , endogenous retrovirus , minigene , gene targeting , viral vector , hek 293 cells , microbiology and biotechnology , virology , computational biology , rna , genetics , transplantation , genome , medicine , recombinant dna , rna splicing , surgery , reproductive biology , embryogenesis
In order to overcome the major immunological barriers to xenotransplantation, genetic strategies have to be developed that ensure long‐term engraftment of the organ. To this end, immune‐modulatory transgenes have to be efficiently expressed and/or the expression of xeno‐relevant porcine genes (xeno‐epitopes) has to be silenced. Viral vectors are powerful tools for modulating expression of foreign genes in organs and even the whole animal. Using lentiviral gene transfer in early embryos, gain‐of‐function models can be generated with high efficacies in pig (lentiviral transgenesis). Through combination of lentiviral transgenesis and RNA interference (RNAi) loss‐of‐function models for xenotransplantation can be generated. Our goal is to combine lentivector‐mediated RNAi directed against α‐galactosyltransferase (α‐GT) with immune‐modulatory approaches to finally generate multitransgenic pigs. Furthermore, sensitivity to human serum inactivation of porcine endogenous retrovirus produced by pig cells with reduced levels of α‐GT expression was analysed.