MicroRNA induction of pluripotential stem cells and uses thereof
View Patent ↗Compositions and methods for inducing the formation of an induced pluripotential stem (iPS) cell from a somatic cell are disclosed. The compositions comprise miR 302-367 cluster and valproic acid. Further disclosed are methods for treatment of a disease or condition in a subject through the use of the compositions.
1. A method of inducing the formation of an induced pluripotential stem (iPS) cell from a non-cancerous somatic cell, the method comprising contacting said somatic cell with a composition comprising a) an isolated nucleic acid comprising a microRNA (miR) 302-367 cluster or a miR 302-367 cluster mimic and b) valproic acid, wherein said composition enhances the induction of the formation of said iPS cell from said non-cancerous somatic cell, wherein formation of said iPS cell is induced from said somatic cell without transducing said somatic cell with a nucleic acid that expresses one or more of Oct3/4, Klf4, Sox2 or c-Myc genes.
2. The method of claim 1 , wherein said miR is operably linked to a regulatory sequence.
3. The method of claim 2 , wherein said regulatory sequence is a constitutive promoter.
4. The method of claim 2 , wherein said regulatory sequence is an inducible promoter.
5. The method of claim 4 , wherein said inducible promoter is a doxycycline inducible promoter.
6. The method of claim 1 , wherein said miR is a miR 302-367 cluster mimic.
7. The method of claim 1 , wherein the nucleic acid sequence encoding said miR is present within a vector.
8. The method of claim 7 , wherein said vector is a viral vector.
9. The method of claim 8 , wherein said viral vector is a lentivirus vector.
10. The method of claim 7 , wherein said vector is a plasmid vector.
11. The method of claim 1 , wherein said somatic cell is a fibroblast cell.
12. The method of claim 1 , wherein said fibroblast cell is an embryonic fibroblast cell.
13. The method of claim 1 , wherein said valproic acid is present in a concentration of 2 mM.
14. The method of claim 1 , wherein the efficiency of said iPS cell formation is at least 10%.
15. A method of increasing the efficiency of nuclear reprogramming of a somatic cell, comprising contacting said somatic cell with a composition comprising a) an isolated nucleic acid comprising a microRNA (miR) 302-367 cluster and b) valproic acid, without transducing said somatic cell with a nucleic acid that expresses one or more of Oct3/4, Klf4, Sox2, or c-Myc genes.
16. A method of enhancing the induction of the formation of an induced pluripotential stem (iPS) cell from a non-cancerous somatic cell, the method comprising contacting said somatic cell with a composition comprising a) an isolated nucleic acid comprising one or more mimics or one or more pre-miRNA precursors associated with a miR 302-367 and b) valproic acid, wherein said composition enhances the induction of the formation of said iPS cell from said non-cancerous somatic cell, wherein formation of said iPS cell is induced from said somatic cell without transducing said somatic cell with a nucleic acid that expresses one or more of Oct3/4, Klf4, Sox2 or c-Myc genes.