US Government As Represented by the Secretary of the Army

The United States of America As Represented by the Department of Health

Kurt R Klimpel

Stephen H Leppla

Yogendra Singh

Naveen Arora

Peter J Nicholls

Peter J Nichols

The present invention provides a nucleic acid encoding a fusion protein comprising a nucleotide sequence encoding the anthrax protective antigen (PA) binding domain of the native anthrax lethal factor (LF) protein and a nucleotide sequence encoding an activity inducing domain of a second protein. Also provided is a nucleic acid encoding a fusion protein comprising a nucleotide sequence encoding the translocation domain and LF binding domain of the native anthrax PA protein and a nucleotide sequence encoding a ligand domain which specifically binds a cellular target. Proteins encoded by the nucleic acid of the invention, vectors comprising the nucleic acids and hosts capable of expressing the protein encoded by the nucleic acids are also provided. A composition comprising the PA binding domain of the native LF protein chemically attached to a non-LF activity inducing moiety is further provided. A method for delivering an activity to a cell is provided. The steps of the method include a) administering to the cell a protein comprising the translocation domain and the LF binding domain of the native PA protein and a ligand domain, and b) administering to the cell a product comprising the PA binding domain of the native LF protein and a non-LF activity inducing moiety, whereby the product administered in step b) is internalized into the cell and performs the activity within the cell. The invention also provides proteins including an anthrax protective antigen which has been mutated to replace the trypsin cleavage site with residues recognized specifically by the HIV-1 protease.

Anthrax toxin fusion proteins and related methods

The present invention provides a nucleic acid encoding a fusion protein, comprising a nucleotide sequence encoding the protective antigen (PA) binding domain of the native lethal factor (LF) protein and a nucleotide sequence encoding an activity inducing domain of a second protein. Also provided is a nucleic acid encoding a fusion protein, comprising a nucleotide sequence encoding the translocation domain and LF binding domain of the native PA protein and a nucleotide sequence encoding a ligand domain which specifically binds a cellular target. Proteins encoded by the nucleic acid of the invention, vectors comprising the nucleic acids and hosts capable of expressing the protein encoded by the nucleic acids are also provided. A composition comprising the PA binding domain of the native LF protein chemically attached to a non-LF activity inducing moiety is further provided. A method for delivering an activity to a cell is provided. The steps of the method include administering to the cell a protein comprising the translocation domain and the LF binding domain of the native PA protein and a ligand domain, and administering to the cell a product comprising the PA binding domain of the native LF protein and a non-LF activity inducing moiety, whereby the product administered is internalized into the cell and performs the activity within the cell.

Anthrax toxin fusion proteins, nucleic acid encoding same

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Gaithersburg, MD, United States of America

Kurt R Klimpel