The present invention relates to compounds, compositions, and methods for
the study, diagnosis, and treatment of traits, diseases and conditions
that respond to the modulation of 11 beta-hydroxysteroid dehydrogenase-1
(11 beta-HSD-1) gene expression and/or activity. The present invention is
also directed to compounds, compositions, and methods relating to traits,
diseases and conditions that respond to the modulation of expression
and/or activity of genes involved in 11 beta-hydroxysteroid
dehydrogenase-1 (11 beta-HSD-1) gene expression pathways or other
cellular processes that mediate the maintenance or development of such
traits, diseases and conditions. Specifically, the invention relates to
double stranded nucleic acid molecules including small nucleic acid
molecules, such as short interfering nucleic acid (siNA), short
interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA),
and short hairpin RNA (shRNA) molecules capable of mediating RNA
interference (RNAi) against 11 beta-hydroxysteroid dehydrogenase-1 (11
beta-HSD-1) gene expression, including cocktails of such small nucleic
acid molecules and lipid nanoparticle (LNP) formulations of such small
nucleic acid molecules. The present invention also relates to small
nucleic acid molecules, such as siNA, siRNA, and others that can inhibit
the function of endogenous RNA molecules, such as endogenous micro-RNA
(miRNA) (e.g, miRNA inhibitors) or endogenous short interfering RNA
(siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of
RISC (e.g., RISC inhibitors), to modulate 11 beta-HSD-1 gene expression
by interfering with the regulatory function of such endogenous RNAs or
proteins associated with such endogenous RNAs (e.g., RISC), including
cocktails of such small nucleic acid molecules and lipid nanoparticle
(LNP) formulations of such small nucleic acid molecules. Such small
nucleic acid molecules and are useful, for example, in providing
compositions to prevent, inhibit, or reduce metabolic diseases traits and
conditions, including but not limited to diabetis (e.g., type I and/or
type II diabetis), insulin resistance, obesity, hypercholesterolemia,
cardiovascular disease and/or other disease states, conditions, or traits
associated with 11 beta-HSD-1 gene expression or activity in a subject or
organism.