Platelets comprising exogenous polypeptides and uses thereof

Abstract

Compositions comprising synthetic membrane-receiver complexes, methods of generating synthetic membrane-receiver complexes, and methods of treating or preventing diseases, disorders or conditions therewith.

What is claimed is: 
     
         1 . A platelet comprising an exogenous polypeptide. 
     
     
         2 . The platelet of  claim 1 , which was produced by a process comprising introducing into the platelet an exogenous nucleic acid encoding the exogenous polypeptide. 
     
     
         3 . The platelet of  claim 1 , which was produced by a process comprising introducing into a nucleated platelet precursor cell an exogenous nucleic acid encoding the exogenous polypeptide. 
     
     
         4 . The platelet of  claim 1 , wherein the nucleated platelet precursor cell is a megakaryocyte, a hematopoietic stem cell, an induced pluripotent stem cell, or an embryonic stem cell. 
     
     
         5 . The platelet of  claim 1 , which was produced by introducing the exogenous polypeptide into the platelet by subjecting the platelet to a controlled cell injury. 
     
     
         6 . The platelet of  claim 5 , wherein the controlled cell injury caused a perturbation in the cell membrane of the platelet. 
     
     
         7 . The platelet of  claim 5 , wherein the controlled cell injury comprises cell deformation, electroporation, sonoporation, liposomal transfection, or salt-based transfection. 
     
     
         8 . The platelet of  claim 5 , wherein the controlled cell injury comprises cell deformation. 
     
     
         9 . The platelet of  claim 5 , wherein the controlled cell injury comprises cell squeezing. 
     
     
         10 . The platelet of  claim 2 , which was produced by introducing the exogenous nucleic acid into the platelet by subjecting the platelet to a controlled cell injury. 
     
     
         11 . The platelet of  claim 10 , wherein the controlled cell injury caused a perturbation in the cell membrane of the platelet. 
     
     
         12 . The platelet of  claim 10 , wherein the controlled cell injury comprises cell deformation, electroporation, sonoporation, liposomal transfection, or salt-based transfection. 
     
     
         13 . The platelet of  claim 10 , wherein the controlled cell injury comprises cell deformation. 
     
     
         14 . The platelet of  claim 10 , wherein the controlled cell injury comprises cell squeezing. 
     
     
         15 . The platelet of  claim 3 , which was produced by introducing the exogenous nucleic acid into the nucleated platelet precursor cell by subjecting the platelet to a controlled cell injury. 
     
     
         16 . The platelet of  claim 15 , wherein the controlled cell injury caused a perturbation in the cell membrane of the nucleated platelet precursor cell. 
     
     
         17 . The platelet of  claim 15 , wherein the controlled cell injury comprises cell deformation, electroporation, sonoporation, liposomal transfection, or salt-based transfection. 
     
     
         18 . The platelet of  claim 3 , which was produced by introducing the exogenous nucleic acid into the nucleated platelet precursor cell using viral transduction. 
     
     
         19 . The platelet of  claim 15 , wherein the controlled cell injury comprises cell squeezing. 
     
     
         20 . The platelet of  claim 3 , wherein the exogenous nucleic acid comprises DNA. 
     
     
         21 . The platelet of  claim 3 , wherein the exogenous nucleic acid comprises RNA. 
     
     
         22 . The platelet of  claim 1 , wherein the exogenous polypeptide comprises an enzyme, a cytokine, an antibody, a hormone, a receptor, or a functional fragment thereof. 
     
     
         23 . The platelet of  claim 1 , wherein the exogenous polypeptide is intracellular. 
     
     
         24 . The platelet of  claim 1 , wherein the exogenous polypeptide is at the surface of the platelet. 
     
     
         25 . The platelet of  claim 1 , wherein the exogenous polypeptide comprises a transmembrane domain. 
     
     
         26 . The platelet of  claim 1 , which comprises at least 1,000 copies of the exogenous polypeptide. 
     
     
         27 . The platelet of  claim 1 , which is a human cell. 
     
     
         28 . A pharmaceutical composition comprising the platelet of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         29 . A method of producing the platelet of  claim 1 , comprising:
 introducing into a nucleated platelet precursor cell an exogenous nucleic acid encoding the exogenous polypeptide; and   culturing the nucleated platelet precursor cell to produce the platelet.   
     
     
         30 . A method of producing the platelet of  claim 1 , comprising introducing into a platelet an RNA molecule encoding the exogenous polypeptide. 
     
     
         31 . A method of producing the platelet of  claim 1 , comprising introducing the exogenous polypeptide into a platelet by subjecting the platelet to a controlled cell injury. 
     
     
         32 . The method of  claim 31 , wherein the controlled cell injury caused a perturbation in the cell membrane of the platelet. 
     
     
         33 . The method of  claim 31 , wherein the controlled cell injury comprises cell deformation, electroporation, sonoporation, liposomal transfection, or salt-based transfection. 
     
     
         34 . The method of  claim 31 , wherein the controlled cell injury comprises cell deformation. 
     
     
         35 . The method of  claim 31 , wherein the controlled cell injury comprises cell squeezing. 
     
     
         36 . A method of treating a disease in a subject in need thereof, the method comprising administering to the subject the platelet of  claim 1 . 
     
     
         37 . The method of  claim 36 , wherein the disease comprises a metabolic disease, a cancer, a clotting disease, or an anti-clotting disease.