METHODS, COMPOSITIONS, AND DEVICES UTILIZING MicroRNA TO DETERMINE PHYSIOLOGICAL CONDITIONS

Abstract

Methods, compositions, and devices are disclosed which use microRNA to detect, predict, treat, and monitor physiological conditions such as disease or injury. microRNA are isolated and their differential expression is measured to provide diagnostic information. This information may then be utilized for evaluation and/or treatment purposes.

What is claimed is: 
     
         1 . A method of detecting or predicting a neurological condition, comprising:
 generating a first microRNA profile from a biological sample, wherein the first microRNA profile comprises the amount of at least one specific microRNA sequence, by:
 receiving the biological sample, the sample being a tissue, serum, or plasma; and 
 isolating microRNA from the biological sample by extracting the microRNA with an organic solvent and obtaining an aqueous phase containing the microRNA, then purifying the aqueous phase through a silica membrane to isolate the microRNA; 
 using hybridization to identify the microRNA sequences; and 
 measuring the amount of at least one specific microRNA sequence; and 
   comparing the amount of the at least one specific microRNA sequence to a reference to provide information for detecting or predicting the neurological condition.   
     
     
         2 . The method of  claim 1 , wherein the at least one specific microRNA sequence is selected from the group consisting of let-7g, miR-298, miR-1, miR-101a*, miR-101b, miR-1224, miR-126-5p, miR-127, miR-128, miR-129-3p, miR-133b, miR-136, miR-138, miR-138*, miR-139-3p, miR-140, miR-140*, miR-142-3p, miR-143, miR-146a, miR-146b, miR-148b, miR-150, miR-15a*, miR-15b, miR-181b, miR-181d, miR-183, miR-185, miR-186, miR-191*, miR-194, miR-19a, miR-200a, miR-200b, miR-200b*, miR-202-3p, miR-206, miR-208a, miR-21, miR-211, miR-221, miR-222, miR-223, miR-27a, miR-27b*, miR-28*, miR-290-5p, miR-291a-5p, miR-297a, miR-299, miR-29b, miR-29c*, miR-301b, miR-302c*, miR-30c, miR-31, miR-322, miR-323-3p, miR-324-3p, miR-324-5p, miR-326, miR-328, miR-331-5p, miR-341, miR-34b-5p, miR-34c*, miR-369-3p, miR-374, miR-376b, miR-379, miR-380-3p, miR-382, miR-384-5p, miR-409-5p, miR-411, miR-411*, miR-423-5p, miR-425, miR-429, miR-434-5p, miR-450b-3p, miR-451, miR-455, miR-465c-3p, miR-466d-5p, miR-467e*, miR-484, miR-486, miR-487b, miR-497, miR-505, miR-511, miR-539, miR-540-3p, miR-551b, miR-568, miR-654-5p, miR-669a, miR-686, miR-688, miR-699, miR-701, miR-706, miR-708, miR-720, miR-721, miR-744*, miR-760, miR-770-5p, miR-7a, miR-7b, miR-881*, miR-93, miR-96, mghv-miR-M1-6, mghv-miR-M1-9, and human orthologs thereof. 
     
     
         3 . The method of  claim 2 , wherein the biological sample is serum or plasma; and further comprising generating a second microRNA profile from cerebrospinal fluid, wherein the second microRNA profile comprises the amount of at least one specific microRNA sequence selected from the group consisting of miR-134, miR-151-5p, miR-223*, miR-302d, miR-325, miR-335*, miR-377*, miR-483-5p, miR-505, miR-509-5p, miR-515-3p, miR-518e, miR-556-3p, miR-589, miR-616*, miR-652, miR-767-3p, miR-873, miR-892a, miR-923, and human orthologs thereof. 
     
     
         4 . The method of  claim 3 , wherein at least two differentially expressed microRNA sequences are identified in the first microRNA profile and at least two differentially expressed microRNA sequences are identified in the second microRNA profile. 
     
     
         5 . The method of  claim 4 , wherein the at least two differentially expressed microRNA sequences in the first microRNA profile are different from the at least two differentially expressed microRNA sequences in the second microRNA profile. 
     
     
         6 . The method of  claim 1 , wherein the at least one specific microRNA sequence is selected from the group consisting of miR-122, miR-124, miR-124a, miR-124b, miR-128a, miR-128b, miR-129, miR-132, miR-134, miR-137, miR-138, miR-149, miR-153, miR-154*, miR-181a, miR-181b, miR-181bN, miR-181c, miR-181d, miR-184, miR-204, miR-213, miR-219, miR-323, miR-324-5p, miR-328, miR-330, miR-338, miR-340, miR-342, miR-348, miR-370, miR-379, miR-383, miR-432, miR-433, miR-485-3p, miR-485-5p, miR-491, miR-9, miR-9*, and human orthologs thereof. 
     
     
         7 . The method of  claim 1 , wherein the at least one specific microRNA sequence is selected from the group consisting of miR-134, miR-151-5p, miR-223*, miR-302d, miR-325, miR-335*, miR-377*, miR-483-5p, miR-505, miR-509-5p, miR-515-3p, miR-518e, miR-556-3p, miR-589, miR-616*, miR-652, miR-767-3p, miR-873, miR-892a, miR-923, and human orthologs thereof. 
     
     
         8 . The method of  claim 1 , wherein the at least one specific microRNA sequence is selected from the group consisting of let-7g, miR-298, miR-1, miR-101a*, miR-101b, miR-1224, miR-126-5p, miR-127, miR-128, miR-129-3p, miR-133b, miR-136, miR-138, miR-138*, miR-139-3p, miR-140, miR-140*, miR-142-3p, miR-143, miR-146a, miR-146b, miR-148b, miR-150, miR-15a*, miR-15b, miR-181b, miR-181d, miR-183, miR-185, miR-186, miR-191*, miR-194, miR-19a, miR-200a, miR-200b, miR-200b*, miR-202-3p, miR-206, miR-208a, miR-21, miR-211, miR-221, miR-222, miR-223, miR-27a, miR-27b*, miR-28*, miR-290-5p, miR-291a-5p, miR-297a, miR-299, miR-29b, miR-29c*, miR-301b, miR-302c*, miR-30c, miR-31, miR-322, miR-323-3p, miR-324-3p, miR-324-5p, miR-326, miR-328, miR-331-5p, miR-341, miR-34b-5p, miR-34c*, miR-369-3p, miR-374, miR-376b, miR-379, miR-380-3p, miR-382, miR-384-5p, miR-409-5p, miR-411, miR-411*, miR-423-5p, miR-425, miR-429, miR-434-5p, miR-450b-3p, miR-451, miR-455, miR-465c-3p, miR-466d-5p, miR-467e*, miR-484, miR-486, miR-487b, miR-497, miR-505, miR-511, miR-539, miR-540-3p, miR-551b, miR-568, miR-654-5p, miR-669a, miR-686, miR-688, miR-699, miR-701, miR-706, miR-708, miR-720, miR-721, miR-744*, miR-760, miR-770-5p, miR-7a, miR-7b, miR-881*, miR-93, miR-96, mghv-miR-M1-6, mghv-miR-M1-9; miR-122, miR-124, miR-124a, miR-124b, miR-128a, miR-128b, miR-129, miR-132, miR-134, miR-137, miR-138, miR-149, miR-153, miR-154*, miR-181a, miR-181b, miR-181bN, miR-181c, miR-181d, miR-184, miR-204, miR-213, miR-219, miR-323, miR-324-5p, miR-328, miR-330, miR-338, miR-340, miR-342, miR-348, miR-370, miR-379, miR-383, miR-432, miR-433, miR-485-3p, miR-485-5p, miR-491, miR-9, miR-9*; miR-134, miR-151-5p, miR-223*, miR-302d, miR-325, miR-335*, miR-377*, miR-483-5p, miR-505, miR-509-5p, miR-515-3p, miR-518e, miR-556-3p, miR-589, miR-616*, miR-652, miR-767-3p, miR-873, miR-892a, miR-923; and human orthologs thereof. 
     
     
         9 . The method of  claim 1 , wherein the at least one specific microRNA sequence is a plurality of microRNA sequences. 
     
     
         10 . The method of  claim 1 , wherein the at least one specific microRNA sequence is selected from the group consisting of let-7g, miR-298, miR-1, miR-101a*, miR-101b, miR-1224, miR-126-5p, miR-127, miR-128, miR-129-3p, miR-133b, miR-136, miR-138, miR-138*, miR-139-3p, miR-140, miR-140*, miR-142-3p, miR-143, miR-146a, miR-146b, miR-148b, miR-150, miR-15a*, miR-15b, miR-181b, miR-181d, miR-183, miR-185, miR-186, miR-191*, miR-194, miR-19a, miR-200a, miR-200b, miR-200b*, miR-202-3p, miR-206, miR-208a, miR-21, miR-211, miR-221, miR-222, miR-223, miR-27a, miR-27b*, miR-28*, miR-290-5p, miR-291a-5p, miR-297a, miR-299, miR-29b, miR-29c*, miR-301b, miR-302c*, miR-30c, miR-31, miR-322, miR-323-3p, miR-324-3p, miR-324-5p, miR-326, miR-328, miR-331-5p, miR-341, miR-34b-5p, miR-34c*, miR-369-3p, miR-374, miR-376b, miR-379, miR-380-3p, miR-382, miR-384-5p, miR-409-5p, miR-411, miR-411*, miR-423-5p, miR-425, miR-429, miR-434-5p, miR-450b-3p, miR-451, miR-455, miR-465c-3p, miR-466d-5p, miR-467e*, miR-484, miR-486, miR-487b, miR-497, miR-505, miR-511, miR-539, miR-540-3p, miR-551b, miR-568, miR-654-5p, miR-669a, miR-686, miR-688, miR-699, miR-701, miR-706, miR-708, miR-720, miR-721, miR-744*, miR-760, miR-770-5p, miR-7a, miR-7b, miR-881*, miR-93, miR-96, mghv-miR-M1-6, mghv-miR-M1-9, and human orthologs thereof. 
     
     
         11 . The method of  claim 1 , wherein the at least one specific microRNA sequence is selected from the group consisting of let-7g, miR-298, miR-101a*, miR-101b, miR-1224, miR-126-5p, miR-128, miR-129-3p, miR-133b, miR-138*, miR-139-3p, miR-140*, miR-146a, miR-148b, miR-15a*, miR-15b, miR-181b, miR-181d, miR-185, miR-186, miR-191*, miR-19a, miR-200b*, miR-202-3p, miR-208a, miR-211, miR-27b*, miR-28*, miR-290-5p, miR-291a-5p, miR-297a, miR-299, miR-29c*, miR-301b, miR-302c*, miR-322, miR-323-3p, miR-324-3p, miR-324-5p, miR-326, miR-328, miR-331-5p, miR-341, miR-34b-5p, miR-34c*, miR-369-3p, miR-374, miR-376b, miR-379, miR-380-3p, miR-382, miR-384-5p, miR-409-5p, miR-411, miR-411*, miR-423-5p, miR-425, miR-429, miR-434-5p, miR-450b-3p, miR-465c-3p, miR-466d-5p, miR-467e*, miR-505, miR-511, miR-539, miR-540-3p, miR-551b, miR-568, miR-654-5p, miR-669a, miR-686, miR-688, miR-699, miR-701, miR-706, miR-720, miR-721, miR-744*, miR-760, miR-770-5p, miR-7a, miR-7b, miR-881*, miR-96, mghv-miR-M1-6, mghv-miR-M1-9, and human orthologs thereof. 
     
     
         12 . A method of using microRNA to monitor a neurological condition, comprising:
 generating a first microRNA profile from a first biological sample of a patient;   administering a treatment to the patient;   generating a second microRNA profile from a second biological sample of the patient;   comparing the second microRNA profile with the first microRNA profile to identify differentially expressed microRNA sequences; and   identifying a change in the neurological condition based on the identity or the amounts of the differentially expressed microRNA sequences.