This invention provides single-stranded and multi-stranded compounds that are useful in various therapeutic modalities to regulate the expression of nucleic acid molecules in a cell. A range of compounds is provided, each containing one or more conformationally restricted nucleomonomers (CRN). In addition, compounds can contain one or more conformationally restricted nucleomonomers and one or more hydroxymethyl substituted nucleomonomers (unlocked nucleomonomers, UNA).

The present invention provides a method of treating cancer in a subject wherein the method comprising administering to the subject an IAP antagonist and a p38 and/or a MK2 inhibitor.

The present invention provides compositions and methods for treating epidermolysis bullosa.

A p38 MAPK inhibitor for use in the treatment or prevention of severe influenza in a human patient. In some embodiments, the severe influenza may be characterised by hypercytokinemia involving elevated levels of one or more pro-inflammatory cytokines. The p38 MAP kinase inhibitor may act to inhibit the release of such pro-inflammatory mediators from endothelial cells. In some embodiments, the p38 MAP kinase inhibitor may inhibit the release of IP 10 from endothelial cells, preferably in a dose-dependent manner.

The present invention provides a method of treating cancer in a subject wherein the method comprising administering to the subject an IAP antagonist and a p38 and/or a MK2 inhibitor.

A p38 MAPK inhibitor for use in the treatment or prevention of severe influenza in a human patient. In some embodiments, the severe influenza maybe characterised by hypercytokinemia involving elevated levels of one or more pro-inflammatory cytokines. The p38 MAP kinase inhibitor may act to inhibit the release of such pro-inflammatory mediators from endothelial cells. In some embodiments, the p38 MAP kinase inhibitor may inhibit the release of IP 10 from endothelial cells, preferably in a dose-dependent manner.

A method of treating a mammalian subject with cancer comprises administering to said subject having a cancer, e.g., a metastatic or refractory cancer or tumor, a small molecule inhibitor of a target signaling molecule of the MEK/MAPK pathway that impairs T cell activation, and administering to said subject a molecule that induces T cell proliferation in the presence of said inhibitor. The combination of a small molecule inhibitor of a target of the MEK/MAPK pathway and the T cell proliferation inducer reduces the proliferation of the cancer and tumor cells in vivo. Compositions and kits including these components are also provided.

An isolated peptide being no longer than 20 amino acids comprising a sequence at least 95% homologous to the sequence GQLNHILGILGX.sub.1PX.sub.2QED (SEQ ID NO: 4), wherein X.sub.1 and X.sub.2 are any amino acid, the peptide being capable of preventing extracellular signal-regulated kinase1/2 (ERK) translocation into the nucleus.

A method of treating a mammalian subject with cancer comprises administering to said subject having a cancer, e.g., a metastatic or refractory cancer or tumor, a small molecule inhibitor of a target signaling molecule of the MEK/MAPK pathway that impairs T cell activation, and administering to said subject a molecule that induces T cell proliferation in the presence of said inhibitor. The combination of a small molecule inhibitor of a target of the MEK/MAPK pathway and the T cell proliferation inducer reduces the proliferation of the cancer and tumor cells in vivo. Compositions and kits including these components are also provided.

An isolated peptide being no longer than 20 amino acids comprising a sequence at least 95% homologous to the sequence GQLNHILGILGX.sub.1PX.sub.2QED (SEQ ID NO: 4), wherein X.sub.1 and X.sub.2 are any amino acid, the peptide being capable of preventing extracellular signal-regulated kinase1/2 (ERK) translocation into the nucleus.