Biologically active molecules for influencing virus-, bacteria-, parasite-infected cells and/or tumor cells and method for the use thereof

Inventors

Poehlmann, Tobias • Guenther, Rolf

Assignees

Bianoscience GmbH • Universitaetsklinikum Jena

Abstract

The aim of the invention is to effectively inhibit virus-, bacteria-, or parasite-infected cells and tumor cells in a targeted manner, even in the case of mutations. According to the invention, biologically active molecules are administered, said biologically active molecules including at least one protease inhibitor for at least one specific target protease of the virus-, bacteria-, or parasite-infected cells and/or tumor cells and at least one peptide-inhibited siRNA, PNA or RNA, the peptide bond of which is broken by the at least one target protease for the purpose of activating the peptide-inhibited siRNA, PNA or RNA. The molecules are used, for example, to influence the gene expression of diseased and infected organs or cells.

Core Innovation

The patent describes biologically active molecules for influencing virus-, bacteria-, or parasite-infected cells and/or tumor cells under conditions in which mutations reduce binding of a protease inhibitor to a specific target protease. The biologically active molecule comprises a protease inhibitor for a specific target protease and a siRNA, PNA or RNA inhibited by a peptide having a peptide bond shared with the siRNA, PNA or RNA. The peptide bond provides a breaking site that is broken by the specific target protease so that the peptide-inhibited siRNA, PNA or RNA is activated.

A preselected protein sequence of the peptide bond is provided for the purpose of activating the peptide-inhibited siRNA, PNA or RNA when the peptide bond shared with the siRNA, PNA or RNA is broken at the breaking site by the specific target protease when the protease inhibitor cannot bind or cannot effectively bind to the specific target protease. The patent explains that the target protease can then activate the peptide-inhibited nucleic acid, leading to suppression of essential gene expression and killing of infected cells, despite residual effects from the protease inhibitor.

The patent further discusses embodiments in which the protease inhibitor and the peptide-inhibited siRNA, PNA or RNA are covalently linked in one molecule, and embodiments in which they are provided as separate covalent or non-covalent complexes delivered with transfection reagents. It also outlines optional functional additions and delivery/administration options, and provides schematic embodiments showing an inhibitor action corresponding to protease inhibition and a nucleic-acid activation action corresponding to peptide bond breaking by the target protease.

Claims Coverage

The partial content provides two independent claims. Across these claims, the core coverage is based on combining protease inhibition with protease-activatable peptide-inhibited siRNA, PNA or RNA, including an embodiment where inhibitor and nucleic acid are covalently combined in one molecule, and a claim directed to using such a composition to influence infected/tumor cells.

The independent claim set is directed to compositions and biologically active molecules that use a specific target protease to activate a peptide-inhibited siRNA/PNA/RNA via a shared, protease-broken peptide bond, thereby enabling nucleic-acid activation when the protease inhibitor cannot bind or cannot effectively bind; one independent claim further requires a covalently bound one-molecule combination of the protease inhibitor and peptide-inhibited nucleic acid.

Stated Advantages

Documented Applications