US2017002317A1PendingUtilityA1

Conversion of non-neuronal cells into neurons

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Individually held — no corporate assignee on recordPriority: Jun 30, 2015Filed: Sep 9, 2016Published: Jan 5, 2017
Est. expiryJun 30, 2035(~8.9 yrs left)· nominal 20-yr term from priority
Inventors:Siddharth G. KamathChad DickeyBasil Cherpelis
C12N 15/86C12N 2501/998C12N 15/1138C12N 2501/999C12N 2310/122C12N 2310/531C12N 2500/34C12N 2506/1307C12N 2501/734A61P 25/28C12N 5/0619C12N 2740/15043G01N 33/5058C12N 15/111A61K 35/30C12N 2310/113C12N 2510/00C12N 15/113C12N 2501/727C12N 2320/30C12N 2506/45C12N 2500/32
38
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Claims

Abstract

The subject invention concerns materials and methods for conversion of non-neuronal cells into neurons. The subject invention also concerns methods for screening drugs and other compounds for activity in treating Alzheimer's disease using neuronal cells produced using the subject invention. The subject invention also concerns neuronal cells that have been produced using the methods of the invention. The subject invention also concerns methods for evaluating therapeutic treatment for efficacy in a person or animal having Alzheimer's disease or other neurodegenerative diseases. The subject invention also concerns methods of treating Alzheimer's disease or other neurodegenerative diseases or conditions in a person or animal.

Claims

exact text as granted — not AI-modified
We claim: 
     
         1 . A neuronal cell produced by conversion of a non-neuronal cell to a neuronal cell by:
 i) incorporating into said non-neuronal cell a polynucleotide of polypyrimidine-tract-binding (PTB) protein short hairpin RNA (shRNA) and a polynucleotide encoding a selectable marker;   ii) selecting for a cell expressing said selectable marker;   iii) culturing said selected cell in a neural induction medium comprising a ROCK inhibitor for a sufficient period of time to induce neuronal development, whereby said selected cell is converted into a neuronal cell.   
     
     
         2 . The neuronal cell according to  claim 1 , wherein said polynucleotide is incorporated into said non-neuronal cell using a virus or viral vector. 
     
     
         3 . The neuronal cell according to  claim 2 , wherein said virus or vector is adenovirus, AAV, retrovirus, or lentivirus. 
     
     
         4 . The neuronal cell according to  claim 1 , wherein said cell is a human cell. 
     
     
         5 . The neuronal cell according to  claim 1 , wherein said non-neuronal cell is a fibroblast cell. 
     
     
         6 . The neuronal cell according to  claim 1 , wherein said neuronal cell expresses one or more of tubulin, MAP2, synapsin, or NeuN. 
     
     
         7 . A method for screening a drug or compound for activity in treating or inhibiting Alzheimer's disease or other neurodegenerative diseases or conditions, comprising providing a neuronal cell produced by converting a non-neuronal cell to a neuronal cell, and contacting said neuronal cell with the drug or compound, and determining whether the drug or compound inhibits formation of Tau protein aggregates in said neuronal cell. 
     
     
         8 . The method according to  claim 7 , wherein said neuronal cell is from a person or animal who may receive the drug or compound. 
     
     
         9 . The method according to  claim 8 , wherein the person or animal has Alzheimer's disease or another neurodegenerative disease or condition. 
     
     
         10 . A method of treating Alzheimer's disease or other neurodegenerative diseases or conditions in a person or animal, comprising providing a neuronal cell produced by converting a non-neuronal cell to a neuronal cell, and administering or implanting said neuronal cell into the person or animal. 
     
     
         11 . The method according to  claim 10 , wherein said neuronal cell is from the person or animal. 
     
     
         12 . The method of  claim 10 , wherein said neuronal cell is administered or implanted into neural tissue. 
     
     
         13 . The method according to  claim 10 , wherein the method further comprises identifying or diagnosing the person or animal as having Alzheimer's disease or other neurodegenerative disease or condition. 
     
     
         14 . The method according to  claim 7 , wherein said neuronal cell expresses one or more of tubulin, MAP2, synapsin, or NeuN. 
     
     
         15 . The method according to  claim 10 , wherein said neuronal cell expresses one or more of tubulin, MAP2, synapsin, or NeuN. 
     
     
         16 . The method according to  claim 7 , wherein said non-neuronal cell is a fibroblast cell. 
     
     
         17 . The method according to  claim 10 , wherein said non-neuronal cell is a fibroblast cell. 
     
     
         18 . The method according to  claim 1 , wherein said ROCK inhibitor is a compound comprising the structure selected from:

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