Biotin complexes for treatment and diagnosis of alzheimer's disease

Abstract

Described herein are compositions and methods for treating or imaging Alzheimer's disease (AD). The compositions comprise a biotin moiety and a siRNA moiety, without the need for a targeting agent such as an antibody, avidin, or streptavidin. In certain embodiments, the compositions further comprise a diagnostic agent.

1 . A composition comprising a biotin moiety and a siRNA moiety, wherein the siRNA moiety comprises a nucleotide selected from the group consisting of: any of SEQ ID NOS:3-15, or a nucleic acid that has at least 85% sequence homology with any one of SEQ ID NOS:3-15. 
     
     
         2 . The composition of  claim 1 , wherein the composition further comprises a linker between the siRNA and the biotin. 
     
     
         3 . The composition of  claim 1 , wherein the composition does not comprise an antibody, an antigen, avidin, or streptavidin. 
     
     
         4 . The composition of  claim 1 , wherein the composition further comprises a diagnostic agent. 
     
     
         5 . The composition of  claim 4 , wherein the diagnostic agent is selected from the group consisting of a fluorophore, a chromophore, a chemoluminescing agent, a radionuclide, an unpair spin atom, a free radical, and a contrast agent. 
     
     
         6 . The composition of  claim 1 , wherein the siRNA moiety comprises a nucleotide selected from the group consisting of: any of SEQ ID NOS:3-8, or a nucleic acid that has at least 85% sequence homology with any one of SEQ ID NOS:3-8. 
     
     
         7 . (canceled) 
     
     
         8 . The composition of  claim 1 , wherein the composition is able to transfect cells in vivo. 
     
     
         9 . The composition of  claim 1 , wherein the composition partially, substantially, or completely deletes, silences, inactivates, interferes with, or down-regulates a gene that encodes a protein involved in AD pathogenesis. 
     
     
         10 . The composition of  claim 9 , wherein the protein involved in AD pathogenesis is selected from the group consisting of amyloid precursor protein, beta amyloid cleaving enzyme-1, Tau, presenilin, selenoprotein P, apolipoprotein E, insulin-degrading protein, neprilysin, and alpha-synuclidin. 
     
     
         11 . The composition of  claim 9 , wherein the gene is selected from the group consisting of MARK2, PAK3, PAK2, ADCK5, AKAP13, LOC55971, PLK2, DYRK1A, MAK, ITK, PIM1, RAGE, ITPK1, CKB, PFKM, DGKB, and SPHK2. 
     
     
         12 . The composition of  claim 9 , wherein the gene is selected from the group consisting of EIF2AK2, CDKL1, DCK, DGKQ, PFKFB3, ERK8, STK19, PRKG2, and PAM2K1IP1. 
     
     
         13 . The composition of  claim 1 , wherein the siRNA moiety comprises a guanosine at the 5′-end. 
     
     
         14 . The composition of  claim 1 , wherein the sense or the antisense strand of the siRNA moiety is equal to or less than 30, 25, 24, 23, 22, 21, 20, 19, 18 or 17 nucleotides in length. 
     
     
         15 . A pharmaceutically acceptable formulation, wherein the pharmaceutically acceptable formulation comprises a therapeutically-effective amount of a composition of  claim 1  and a pharmaceutically acceptable carrier or diluent. 
     
     
         16 . A method of treating Alzheimer's disease in a mammal, comprising the step of: administering to said mammal a therapeutically effective amount of a composition of  claim 1 . 
     
     
         17 . The method of  claim 16 , wherein said mammal is a human. 
     
     
         18 . A method generating an image of a subject, comprising the steps of:
 administering to a subject in need of imaging a detectable amount of a composition of  claim 4 , and   generating an image.   
     
     
         19 . The method of  claim 18 , wherein said subject is a human. 
     
     
         20 . A method of treating Alzheimer's disease in a mammal, comprising the step of:
 administering to said mammal a therapeutically effective amount of a composition comprising a biotin moiety and a siRNA moiety, wherein the siRNA moiety comprises a nucleotide of SEQ ID NO: 1 or a nucleic acid that has at least 95% sequence homology with SEQ ID NO: 1.   
     
     
         21 . (canceled) 
     
     
         22 . A method generating an image of a subject, comprising the steps of:
 administering to a subject in need of imaging a detectable amount of a composition comprising a diagnostic agent, a biotin moiety, and a siRNA moiety, wherein the siRNA moiety comprises a nucleotide of SEQ ID NO: 1 or a nucleic acid that has at least 95% sequence homology with SEQ ID NO: 1, and   generating an image.   
     
     
         23 . (canceled)