Compositions and methods for binding agglomeration proteins

Abstract

Amplibody compositions and methods used to interact with agglomeration proteins are disclosed herein. Compositions herein comprise one or more DNA or RNA molecules having affinity for at least one agglomeration protein. The nucleic acid component is a naturally or non-naturally occuring molecule with twenty or more ribonucleotide bases. For RNA, at least one nucleotide sequence portion of this RNA molecule has affinity to at least one consensus sequence present in the agglomeration RNA-binding protein. The portion of nucleotide sequence of RNA having affinity for agglomeration proteins is a sequence that is derived from either and RNA virus, and RNA agglomeration proteins is a sequence that is derived from either and RNA virus, an RNA phage, a messenger RNA (“mRNA”), a ribosomal RNA (“rRNA”), a transfer RNA (“tRNA”), a sequence that is received as a template by one or more RNA dependent RNA polymerases, or a combination thereof. Methods disclosed herein are directed towards detecting the presence of one or more agglomeration proteins in a sample matrix using the amplibody compositions described herein.

What is claimed is:  
     
         1 . A composition having affinity for one or more agglomeration proteins, comprising: 
 a non-naturally occurring RNA with twenty (20) or more nucleotides, wherein at least one sequence portion of said nucleotides has affinity for said one or more agglomeration proteins, and wherein said at least one sequence portion of said nucleotides is selected from the group consisting of: 
 (a) a nucleotide sequence derived from an RNA virus,  
 (b) a nucleotide sequence derived from an RNA phage,  
 (c) a nucleotide sequence that is received as a template by one or more RNA dependent RNA polymerases,  
 (d) a nucleotide sequence derived from a messenger RNA,  
 (e) a nucleotide sequence derived from a ribosomal RNA,  
 (f) a nucleotide sequence derived from a transfer RNA, and  
 (g) a combination thereof.  
   
     
     
         2 . The composition of  claim 1 , wherein said non-naturally occurring RNA has at least one loop having at least three guanine nucleotides in series.  
     
     
         3 . The composition of  claim 1 , wherein said at least one sequence portion of said nucleotides having affinity for said one or more agglomeration proteins is from about 20 to about 10,000 nucleotides in length.  
     
     
         4 . The composition of  claim 1 , wherein said RNA virus is a retrovirus.  
     
     
         5 . The composition of  claim 1 , wherein said virus is selected from the group consisting of human immunodeficiency virus, polio virus, influenza virus, small pox virus, chicken pox virus, herpes virus, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, feline leukemia virus, human T-cell leukemia virus, simian immunodeficiency virus, and combinations thereof.  
     
     
         6 . The composition of  claim 1 , wherein said RNA dependent RNA polymerase is selected from the group selected from Q-beta replicase and Q-Amp.  
     
     
         7 . The composition of  claim 1 , wherein said nucleotide sequence that is received as a template for one or more RNA dependent RNA polymerases is selected from the group consisting of midi-variant RNA, mini-variant RNA, RQ RNA, and combinations thereof.  
     
     
         8 . The composition of  claim 7 , wherein said RQ RNA is RQ11+12 RNA.  
     
     
         9 . A method for detecting agglomerated protein within a sample, comprising: 
 forming an affinity complex by contacting said sample with a probe, wherein said probe is a non-naturally occurring RNA with twenty (20) or more nucleotides, wherein at least one sequence portion of said nucleotides has an affinity for said one or more agglomeration proteins, and wherein said at least one sequence portion of said nucleotides is selected from the group consisting of: 
 (a) a nucleotide sequence derived from an RNA virus,  
 (b) a nucleotide sequence derived from an RNA phage,  
 (c) a nucleotide sequence that is received as a template by one or more RNA dependent RNA polymerases,  
 (d) a nucleotide sequence derived from a messenger RNA,  
 (e) a nucleotide sequence derived from a ribosomal RNA,  
 (f) a nucleotide sequence derived from a transfer RNA, and  
 (g) a combination thereof; and  
   detecting said affinity complex, and wherein said detection of said affinity complex is indicative of one or more agglomeration proteins present in said sample.    
     
     
         10 . The method of  claim 9 , wherein said sample is contacted with at least two probes, wherein each probe binds to a different binding loci on said one or more agglomeration proteins.  
     
     
         11 . The method of  claim 10 , wherein said at least two probes has a first probe, and wherein said first probe is immobilized to a solid support.  
     
     
         12 . The method of  claim 11 , wherein said solid support is selected from the group consisting of a gel, glass, plastic, cellulose, magnetic beads, membranes, latex beads, silica, chromatographic support, polymeric materials, and wax-based.  
     
     
         13 . The method of  claim 12 , wherein said gel is selected from the group consisting of polyacrylamide, starch, and agarose.  
     
     
         14 . The method of  claim 11 , wherein at least one of said at least two probes is labeled.  
     
     
         15 . The method of  claim 14 , wherein said label is selected from the group consisting of radioactive isotopes, affinity reagents, such as biotin, intercalating fluorescent dyes, fluorescent moiety attached to affinity composition, phosphorescent dyes, electrophores, chemiluminescent chromophores, and combinations thereof.  
     
     
         16 . The method of  claim 10 , wherein said detecting said affinity complex is accomplished by a method of detection selected from the group consisting of mass or density measurement, mass spectrometry, plasmon resonance, optical emission or absorption, fluorescence, phosphorescence, luminescence, chemiluminescence, polarization, refractive index changes, electrical conductivity, radioactivity, viscosity, turbidity, and optical rotation.  
     
     
         17 . The composition of  claim 10 , wherein said at least one sequence portion of said nucleotides having affinity for said one or more agglomeration proteins is from about 20 to about 10,000 nucleotides in length.  
     
     
         18 . A kit for determining the presence or absence of one or more agglomeration proteins within a sample, comprising: one or more probes, wherein said one or more probes comprises a non-naturally occurring RNA with twenty (20) or more nucleotides, wherein at least one sequence portion of said nucleotides has affinity for said one or more agglomeration proteins, and wherein said at least one sequence portion of said nucleotides is selected from the group consisting of: 
 (i) a nucleotide sequence derived from an RNA virus,    (ii) a nucleotide sequence derived from an RNA phage,    (iii) a nucleotide sequence that is received as a template by one or more RNA dependent RNA polymerases,    (iv) a nucleotide sequence derived from a messenger RNA,    (v) a nucleotide sequence derived from a ribosomal RNA,    (vi) a nucleotide sequence derived from a transfer RNA, and    (vii) a combination thereof.    
     
     
         19 . The kit of  claim 18 , wherein at least one of said one or more probes is labeled.  
     
     
         20 . The kit of  claim 18 , wherein said kit comprises at least two probes.  
     
     
         21 . The kit of  claim 20 , wherein at least one of said at least two affinity probes is labeled.  
     
     
         22 . The kit of  claim 20 , wherein each of said at least two probes binds to one or more agglomeration proteins at different sites.  
     
     
         23 . The kit of  claim 20 , wherein said at least two probes has a first probe, and wherein said first probe is immobilized to a solid support.  
     
     
         24 . The composition of  claim 18 , wherein said at least one sequence portion of said nucleotides having affinity for said one or more agglomeration proteins is from about 20 to about 10,000 nucleotides in length.