Abstract: The present invention provides methods of modulating the activation of certain Toll-like receptors (TLRs) such as TLR7/8 using chemically modified nucleic acid molecules. The present invention also provides methods of using such modified nucleic acid molecules to treat diseases or disorders associated with TLR7/8 activation such as systemic lupus erythematosus. The present invention further provides compositions comprising a combination of modified nucleic acid molecules and nucleic acid molecules that silence expression of one or more target sequences. Methods of using such compositions to reduce or abolish target gene expression without inducing cytokine production are also provided.

Abstract: The present invention provides chemically modified siRNA molecules and methods of using such siRNA molecules to silence target gene expression. Advantageously, the modified siRNA of the present invention is less immunostimulatory than its corresponding unmodified siRNA sequence and retains RNAi activity against the target sequence. The present invention also provides nucleic acid-lipid particles comprising a modified siRNA, a cationic lipid, and a non-cationic lipid, which can further comprise a conjugated lipid that inhibits aggregation of particles. The present invention further provides methods of silencing gene expression by administering a modified siRNA to a mammalian subject. Methods for identifying and/or modifying an siRNA having immunostimulatory properties are also provided.

Abstract: The present invention provides methods for minimizing or inhibiting immune responses to immunostimulatory nucleic acids by pretreating with one or more doses of a glucocorticoid prior to nucleic acid administration. The nucleic acids are typically administered using a lipid-based carrier system such as a nucleic acid-lipid particle or liposome. As a result, patients following a glucocorticoid dosing regimen advantageously benefit from nucleic acid therapy without suffering any of the immunostimulatory side-effects associated with such therapy.

Abstract: The present invention provides nucleic acid-lipid particles comprising siRNA molecules that silence ApoB expression and methods of using such nucleic acid-lipid particles to silence ApoB expression.

Abstract: The present invention provides siRNA molecules and methods of using such siRNA molecules to modulate an immune response and to silence expression of a target gene.