Methods and compositions related to induced sensory neurons

Patent metadata

Field	Value
Publication number	US-2016333311-A1
Application number	US-201415106460-A
Country	US
Kind code	A1
Filing date	Dec 19, 2014
Priority date	Dec 20, 2013
Publication date	Nov 17, 2016
Grant date	—

Abstract

This invention provides methods of generating induced sensory neurons (iSNs) from non-neuronal cells such as fibroblasts. The invention also provides methods of using iSNs in various therapeutic or non-therapeutic applications, e.g., methods to identify agents or cellular modulations that enhance iSN formation from non-neuronal cells.

First claim

1 . A method for generating induced sensory neurons (iSNs), comprising co-expressing in a non-neuronal cell a combination of Brn3AlNgn1 genes or Brn3AlNgn2 genes, thereby generating induced sensory neurons.

2 . The method of claim 1 , wherein expression of the Brn3AlNgn1 genes or Brn3AlNgn2 genes is temporal.

3 . The method of claim 2 , wherein temporal expression of the Brn3AlNgn1 genes or Brn3AlNgn2 genes is via inducible expression.

4 . The method of claim 1 , wherein the non-neuronal cell is a fibroblast, an embryonic stem cell (ESC), or an induced pluripotent stem cell (iPSC).

5 . The method of claim 1 , wherein the non-neuronal cell is an embryonic fibroblast or an adult fibroblast.

6 . The method of claim 5 , wherein the fibroblast is derived from a mammal.

7 . The method of claim 6 , wherein the mammal is human, mouse or rat.

8 . The method of claim 1 , wherein the Brn3AlNgn1 genes or Brn3AlNgn2 genes are transiently expressed in the non-neuronal cell.

9 . The method of claim 1 , wherein the Brn3A gene and the Nng1 gene are co-expressed in the non-neuronal cell.

10 . The method of claim 1 , wherein the Brn3A gene and the Ngn2 gene are co-expressed in the non-neuronal cell.

11 . The method of claim 1 , wherein an expression vector harboring the Brn3A gene and the Nng1 or Ngn2 gene is introduced into the non-neuronal cell.

12 . The method of claim 11 , wherein the expression vector is a lentiviral vector.

13 . The method of claim 1 , further comprising examining the induced sensory neurons for the presence of a neuronal marker.

14 . An induced sensory neuron generated in accordance with claim 1 .

15 . An isolated cell comprising one or more expression vectors that express a combination of Brn3AlNgn1 genes or Brn3AlNgn2 genes.

16 . The cell of claim 15 , which is a non-neuronal cell.

17 . The cell of claim 15 , which is a fibroblast, an embryonic stem cell (ESC), or an induced pluripotent stem cell (iPSC).

18 . (canceled)

19 . (canceled)

20 . (canceled)

21 . (canceled)

22 . (canceled)

23 . A method for treating in a subject a neurological condition or disorder that is associated with or mediated by a loss or degeneration of sensory neurons, comprising (1) obtaining a non-neuronal cell from the subject in need of treatment; (2) generating a population of induced sensory neurons (iSNs) from said non-neuronal cell by co-expressing in the non-neuronal cell a combination of Brn3AlNgn1 genes or Brn3AlNgn2 genes; and (3) administering a therapeutically effective amount of the iSN population to the subject, thereby treating the neurological condition or disorder in the subject.

24 . (canceled)

25 . The method of claim 23 , wherein the non-neuronal cell is a fibroblast, an embryonic stem cell (ESC), or an induced pluripotent stem cell (iPSC).

26 . (canceled)

27 . The method of claim 23 , wherein the subject is human.

28 - 39 . (canceled)

Assignees

• Blanchard Joel W
• Eade Kevin T
• Baldwin Kristin
• Scripps Research Inst

Inventors

• Blanchard Joel W
• Eade Kevin T
• Baldwin Kristin

Classifications

• C12N2506/13

  from connective tissue cells, from mesenchymal cells · CPC title

• C12N2501/60

  Transcription factors · CPC title

• C12N2506/02

  from embryonic cells · CPC title

• C12N2506/45

  from artificially induced pluripotent stem cells · CPC title

• C12N2510/00

  Genetically modified cells · CPC title