Method and device for purification of blood from circulating cell free dna

Abstract

The invention provides apheresis devices and their use for removal of substantially all types of cell free DNA (cfDNA) in patients' blood, including nucleosome-bound cfDNA, exosome-bound cfDNA and unbound cfDNA (including double stranded DNA (dsDNA), single stranded DNA (ssDNA) and oligonucleotides), to limit the negative effects of the circulating cfDNA and to treat various diseases.

1 - 54 . (canceled) 
     
     
         55 . A device comprising one or more affinity matrices, wherein said one or more affinity matrices are capable of capturing nucleosome-bound cell free DNA (cfDNA), exosome-bound cfDNA, and unbound cfDNA from fluid of a subject, wherein at least one of the one or more affinity matrices comprises an antinucleosome antibody. 
     
     
         56 . The device of  claim 55 , configured to perform apheresis. 
     
     
         57 . The device of  claim 55 , wherein the fluid is blood or plasma. 
     
     
         58 . The device of  claim 55 , wherein the unbound cfDNA comprises dsDNA, ssDNA and oligonucleotides. 
     
     
         59 . The device of  claim 55 , wherein the device comprises two or more affinity matrices. 
     
     
         60 . The device of  claim 59 , wherein (i) the first one or more affinity matrices is capable of capturing nucleosome-bound cell free DNA (cfDNA) and/or exosome-bound cfDNA and (ii) the second one or more affinity matrices is capable of capturing unbound cfDNA, and wherein the first and second affinity matrices are arranged within the device in any order. 
     
     
         61 . The device of  claim 55 , wherein the device comprises a single affinity matrix. 
     
     
         62 . The device of  claim 59 , wherein at least one of the affinity matrices comprises DNA binding polymer. 
     
     
         63 . The device of  claim 62 , wherein the DNA binding polymer is selected from a polyamidoamine (PAMAM) dendrimer, Poly-L-lysine, polyvinylpyrrolidone, and polyethyleneimine. 
     
     
         64 . The device of  claim 55 , wherein the antinucleosome antibody is immobilized to polysaccharide beads. 
     
     
         65 . A system for extracorporeal treatment of fluid, by reduction of the level of circulating cfDNA, which system comprises an extracorporeal circuit, comprising the device according to  claim 55 . 
     
     
         66 . The system of  claim 65 , wherein the fluid is blood. 
     
     
         67 . A method of reducing the level of cell free DNA (cfDNA) in the blood of a subject, the method comprising:
 (a) performing an apheresis procedure comprising diverting blood or plasma from the subject into the apheresis device of  claim 55  or the system of  claim 65  to produce blood or plasma with reduced levels of the cfDNA; and   (b) returning the blood or plasma with reduced levels of the cfDNA to the subject,   wherein the apheresis procedure reduces the level of nucleosome-bound cfDNA, exosome-bound cfDNA, and unbound cfDNA in the blood of the subject.   
     
     
         68 . A method of treating a disease in a subject in need thereof, the method comprising:
 (a) performing an apheresis procedure comprising diverting blood or plasma from the subject into the apheresis device of  claim 55  or the system of  claim 65  to produce blood or plasma with reduced levels of the cfDNA; and   (b) returning the blood or plasma with reduced levels of the cfDNA to the subject,   wherein the apheresis procedure reduces the level of nucleosome-bound cfDNA, exosome-bound cfDNA, and unbound cfDNA in the blood of the subject.   
     
     
         69 . The method of  claim 67 , wherein the subject has a disease characterized by elevated level of cfDNA in the blood. 
     
     
         70 . The method of  claim 69 , wherein the disease is selected from the group consisting of a neurodegenerative disease, a cancer, a chemotherapy-related toxicity, an irradiation induced toxicity, an organ failure, an organ injury, an organ infarct, ischemia, an acute vascular event, a stroke, graft-versus-host-disease (GVHD), graft rejection, sepsis, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), a traumatic injury, aging, diabetes, atherosclerosis, an autoimmune disorder, eclampsia, infertility, a pregnancy-associated complication, a coagulation disorder, and an infection. 
     
     
         71 . The method of  claim 68 , wherein the subject has a disease characterized by elevated level of cfDNA in the blood. 
     
     
         72 . The method of  claim 71 , wherein the disease is selected from the group consisting of a neurodegenerative disease, a cancer, a chemotherapy-related toxicity, an irradiation induced toxicity, an organ failure, an organ injury, an organ infarct, ischemia, an acute vascular event, a stroke, graft-versus-host-disease (GVHD), graft rejection, sepsis, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), a traumatic injury, aging, diabetes, atherosclerosis, an autoimmune disorder, eclampsia, infertility, a pregnancy-associated complication, a coagulation disorder, and an infection.