United States Patent:  6,043,339

Assignee:  Vanderbilt University (Nashville, TN)

Filed:  October 13, 1998

The present invention relates to the delivery of biologically active molecules, such as peptides, nucleic acids and therapeutic agents, into the interior of cells by administering to the cells a complex comprising the molecule linked to an importation competent signal peptide. Such delivery can be utilized for purposes such as peptide therapy, gene transfer, and antisense therapy.

SUMMARY OF THE INVENTION

The present invention provides a method of importing a biologically active molecule into a cell ex vivo comprising administering to the cell, under import conditions, a complex comprising the molecule linked to an importation competent signal peptide, thereby importing the molecule into the cell. Molecules that can be delivered by this method can include, for example, peptides, polypeptides, proteins, nucleic acids, carbohydrates, lipids, glycolipids, and therapeutic agents.

The present invention further provides a method of importing a biologically active molecule into a cell in a subject comprising administering to the subject a complex comprising the molecule linked to an importation competent signal peptide, thereby importing the molecule into the cell of the subject.

Additionally, the instant invention provides a method of importing a biologically active molecule into the nucleus of a cell in a subject comprising administering to the subject a complex comprising the molecule linked to an importation competent signal peptide and a nuclear localization peptide, thereby importing the molecule into the nucleus of the cell of the subject.

Further, the present invention provides a method of regulating growth of a cell in a subject comprising administering to the subject a complex comprising a growth regulatory peptide linked to an importation competent signal peptide to import the growth regulatory peptide into the cell of the subject, thereby regulating the growth of the cell.

The present invention additionally provides a method of inhibiting expression in a cell in a subject of a gene controlled by transcription factor NF-.kappa.B comprising administering to the subject a complex comprising an importation competent signal peptide linked to a nuclear localization peptide of an active subunit of NF-.kappa.B complex.

Also, the present invention provides a method of stimulating the immune system of a subject comprising administering to the subject a complex comprising an importation competent signal peptide linked to an antigenic peptide.

The instant invention also provides a complex comprising a biologically active molecule linked to an importation competent signal peptide and to a nuclear localization peptide.

The present invention further provides a complex comprising an importation competent signal peptide linked to a biologically active molecule selected from the group consisting of a nucleic acid, a carbohydrate, a lipid, a glycolipid and a therapeutic agent.

The present invention also provides a method of screening signal peptides for the ability to effect the importation of a biologically active molecule into a cell comprising administering to the cell a complex comprising the molecule linked to the signal peptide and determining whether the molecule is imported into the cell, the presence of importation of the molecule indicating a signal peptide which can effect importation.

Claim 1 of 10 Claims

1. A complex comprising a biologically active molecule selected from the group consisting of polypeptides and nucleic acids, linked to an importation competent signal peptide and to a nuclear localization peptide, wherein the amino acid or nucleotide sequence of the biologically active molecule, the importation competent signal peptide, and the nuclear localization peptide are not derived from the same gene.

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