Silencing of gene expression by RNA interference (RNAi) has become a powerful tool for
functional genomics in mammalian cells. Furthermore, RNAi holds promise as a simple, fast
and cost-effective approach to studying mammalian gene function in vivo and as a novel
therapeutic approach. This review provides an overview of the progress of RNAi in vivo, with
emphasis on systemic/local siRNA delivery, viral shRNA vectors, shRNA vector transgenic
mice and conditional systems to control shRNA vectors. Taken together, the data from 80 in …

The CTLA4 gene is important for T lymphocyte-mediated immunoregulation and has been
associated with several autoimmune diseases, in particular, type 1 diabetes. To model the
impact of natural genetic variants of CTLA4, we constructed RNA interference
(RNAi)“knockdown” mice through lentiviral transgenesis. Variegation of expression was
observed in founders but proved surmountable because it reflected parental imprinting, with
derepression by transmission from male lentigenics. Unlike the indiscriminate multiorgan …

The discovery that small interfering RNA duplexes (siRNA) can silence gene expression in
mammalian cells has revolutionized biomedical research. The most successful application
of the discovery has been to study gene function in cultured human or mouse cells.
However, the knockdown effect of siRNA is only transient. To achieve a more sustained
gene-silencing effect, shRNA (small hairpin RNA) expressed from a vector is preferred. An
additional benefit of shRNA is that RNA interference (RNAi) can now be applied in vivo …