US 12,472,270 B2
Methods and compositions for reprogramming Müller Glia
Thomas A. Reh, Seattle, WA (US); Nikolas L. Jorstad, Seattle, WA (US); and Levi Todd, Seattle, WA (US)
Assigned to UNIVERSITY OF WASHINGTON, Seattle, WA (US)
Appl. No. 17/594,661
Filed by UNIVERSITY OF WASHINGTON, Seattle, WA (US)
PCT Filed Apr. 29, 2020, PCT No. PCT/US2020/030407
§ 371(c)(1), (2) Date Oct. 25, 2021,
PCT Pub. No. WO2020/223308, PCT Pub. Date Nov. 5, 2020.
Claims priority of provisional application 62/840,264, filed on Apr. 29, 2019.
Prior Publication US 2022/0193265 A1, Jun. 23, 2022
Int. Cl. A61K 48/00 (2006.01); A61K 38/17 (2006.01); A61P 27/02 (2006.01); C12N 15/62 (2006.01); C12N 15/86 (2006.01)
CPC A61K 48/0058 (2013.01) [A61K 38/1709 (2013.01); A61P 27/02 (2018.01); C12N 15/62 (2013.01); C12N 15/86 (2013.01); C12N 2740/15043 (2013.01); C12N 2750/14143 (2013.01)] 18 Claims
 
1. A method for inducing retinal regeneration in a mammalian subject comprising: administering to a retina of the subject a nucleic acid molecule comprising a nucleic acid sequence encoding two or more proneural bHLH transcription factors, wherein expression of the proneural bHLH transcription factors stimulates regeneration of retinal interneurons from retinal Müller glia (MG) and reprograms the MG into bipolar, amacrine, horizontal, and/or ganglion cells, wherein the proneural bHLH transcription factors comprise Ascl1 and a second proneural bHLH transcription factor selected from the group consisting of Atoh7, Atoh1 Neurogenin-2, and Neuronal Differentiation 1 (Neurod1).