High efficiency tissue specific compound delivery system using streptavidin-protein a fusion protein
AssigneeNew York University
InventorsDaniel Meruelo, Kouichi Ohno, Brandi A. Levin
Life of this patent
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Abstract
The present invention relates to methods and compositions that can be employed to introduce toxins and nucleic acids into the cytoplasm or nucleus of a eukaryotic cell, particularly a cell of a higher vertebrate. The invention particularly concerns the use of a fusion protein of streptavidin and protein A sequences to form a non-covalent complex of a toxin or nucleic acid and an antibody.
Claims26
A complex for transferring a compound into a cell, which comprises:
- (a) a streptavidin-protein A fusion protein having an antibody binding site and a biotin binding site;
- (b) an antibody, bound to the antibody binding site, which antibody is specific for a cell surface protein, and which cell surface protein undergoes endocytosis after binding with the antibody;
- and
- (c) a biotinylated compound, bound to the biotin binding site.
A complex for transferring a prodrug into a cell, which comprises:
- (a) a streptavidin-protein A fusion protein having an antibody binding site and a biotin binding site;
- (b) an antibody, bound to the antibody binding site, which antibody is specific for a cell surface protein, and which cell surface protein undergoes endocytosis after binding with the antibody;
- and
- (c) a biotinylated prodrug, bound to the biotin binding site.
A complex for transferring a multidrug resistance (MDR) gene product into a cell, which comprises:
- (a) a streptavidin-protein A fusion protein having an antibody binding site and a biotin binding site;
- (b) an antibody, bound to the antibody binding site, which antibody is specific for a cell surface protein, and which cell surface protein undergoes endocytosis after binding with the antibody;
- and
- (c) a biotinylated MDR gene product, bound to the biotin binding site.
A complex for transferring a single stranded nucleic acid into a cell, which comprises:
- (a) a streptavidin-protein A fusion protein having an antibody binding site and a biotin binding site;
- (b) an antibody, bound to the antibody binding site, which antibody is specific for a cell surface protein, and which cell surface protein undergoes endocytosis after binding with the antibody;
- and
- (c) a biotinylated single stranded nucleic acid, bound to the biotin binding site.
A complex for transferring a duplex nucleic acid into a cell, which comprises:
- (a) a streptavidin-protein A fusion protein having an antibody binding site and a biotin binding site;
- (b) an antibody, bound to the antibody binding site, which antibody is specific for a cell surface protein, and which cell surface protein undergoes endocytosis after binding with the antibody;
- (c) a biotinylated single stranded nucleic acid, having a homopurine or homopyrimidine portion, bound to the biotin binding site;
- and
- (d) a double stranded DNA that forms triplex structure with the biotinylated single stranded nucleic acid.
A complex for transferring protein of a pathological bacteria or virus into a cell, which comprises:
- (a) a streptavidin-protein A fusion protein having an antibody binding site and a biotin binding site;
- (b) an antibody, bound to the antibody binding site, which antibody is specific for a cell antigen presenting cell surface protein, and which cell surface protein undergoes endocytosis after binding with the antibody;
- and
- (c) a biotinylated protein of a pathological bacteria or virus, bound to the biotin binding site.
A method for transferring a compound into a cell, which comprises the steps of:
- (a) forming a complex comprising
- i) a streptavidin-protein A fusion protein having an antibody binding site and a biotin binding site;
- ii) an antibody, bound to the antibody binding site, which antibody is specific for a cell surface protein, and which cell surface protein undergoes endocytosis after binding with the antibody;
- and
- iii) a biotinylated compound, bound to the biotin binding site;
- (b) isolating the complex from the biotinylated compound that is not bound to the biotin binding site;
- and
- (c) exposing the isolated complex to a cell, so that the compound enters the cell.
A method for transferring double stranded DNA into a cell, which comprises the steps of:
- (a) forming a complex comprising:
- i) a streptavidin-protein A fusion protein having an antibody binding site and a biotin binding site;
- ii) an antibody, bound to the antibody binding site, which antibody is specific for a cell surface protein, and which cell surface protein undergoes endocytosis after binding with the antibody;
- iii) a biotinylated single stranded nucleic acid, bound to the biotin binding site;
- and
- iv) a double stranded DNA that forms triplex structure with the biotinylated single stranded nucleic acid;
- and
- (b) exposing the complex to a cell, so that the double stranded DNA enters the cell.
Dependencies are inferred from the claim text.