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Nuclear targeting by means of bacterial proteins

a technology of bacterial proteins and nuclei, which is applied in the direction of macromolecular non-active ingredients, peptides, drug compositions, etc., can solve the problem that protein h simply diffuses through the cytoplasm and cannot be excluded, so as to prevent cell proliferation and combat tumours

Inactive Publication Date: 2008-04-10
HANSA MEDICAL AB
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent text describes a new property of a protein called protein H, which can be targeted to the nucleus of a cell. This can be useful for delivering drugs or other molecules to the nucleus for treating diseases such as cancer. The invention provides a nuclear delivery construct that includes protein H or a fragment or derivative thereof, which is targeted to the nucleus of a eukaryotic cell. This construct can be used in pharmaceutical compositions and in methods of treating or diagnosing diseases of the human or animal body. The technical effect of this invention is the ability to target specific molecules to the nucleus of a cell for therapeutic purposes.

Problems solved by technology

However, the possibility that protein H simply diffuses through the cytoplasm cannot be excluded.

Method used

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  • Nuclear targeting by means of bacterial proteins
  • Nuclear targeting by means of bacterial proteins
  • Nuclear targeting by means of bacterial proteins

Examples

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example

[0109] The following Example illustrates the invention.

Summary

[0110] Some strains of the human pathogen Streptococcus pyogenes express a surface protein called protein H, which is released from the streptococcal surface by a cysteine proteinase produced by the bacteria. Here we find that soluble protein H binds to the surface of lymphocytes and granulocytes. The molecule is taken up by lymphocytes and transported to the nucleus through a previously unknown intracellular pathway. In the cytoplasm, protein H was found to bind to actin whereas when proteins were solubilised from membrane fractions by papain, protein H was found to interact with nucleophosmin / B23, a protein known to shuttle between the nucleus and the cytoplasm. In the nucleus, protein H is dissociated from nucleophosmin / B23 and instead forms complexes with the nuclear proteins SET and hnRNP A2 / B1, resulting in nuclear accumulation of protein H and a cytostatic effect.

Experimental Procedures

Bacterial Strain, Prot...

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Abstract

A nuclear delivery construct comprises (i) protein H or a fragment or derivative thereof that is capable of being targeted to the nucleus of a eukaryotic cell; and associated therewith (ii) one or more other components whose targeting to the nucleus of the eukaryotic cell is desired.

Description

[0001] This application is a continuation of U.S. patent application Ser. No. 09 / 569,349 filed May 11, 2000, which is a continuation under 35 U.S.C. § 111 (a) of International Patent Application No. PCT / GB98 / 03385, with an international filing date of Nov. 11, 1998, which application claims the benefit of United Kingdom Patent Application No. 9723825.7, filed Nov. 11, 1997, the entire disclosure of these applications are hereby incorporated herein by reference.FIELD OF THE INVENTION [0002] The present invention relates to nuclear targeting by means of bacterial proteins. It is based on the finding that protein H, which can be derived from Streptococcus pyogenes, is targeted to the nuclei of eukaryotic cells, specifically lymphocytes. The present invention therefore relates to nuclear targeting constructs comprising protein H, or a fragment or derivative thereof, associated with another component whose targeting to the nucleus is desired. It also relates to uses of such nuclear targe...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/00A61P31/00A61P35/00C07H21/04C07K1/00C12N15/00C12N5/00A61K31/711C12N15/09A61K47/42A61K47/48A61K48/00A61P31/12C07K14/315C12N5/10C12N15/90C12P21/02C12R1/46
CPCA61K48/00Y10S530/82C12N15/90A61P31/00A61P31/12A61P35/00
Inventor AXCRONA, EUGEN J.K.BJORCK, LARS H.FRICK, INGA-MARIALEANDERSSON, TOMAS B.
Owner HANSA MEDICAL AB