Methods and compositions to stimulate retinal regeneration
AssigneeUniversity of Washington
InventorsThomas A. REH, Nikolas L. JORSTAD, Stefanie G. WOHL
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Abstract
Methods and compositions are provided for regeneration of retinal neurons and vision restoration after injury, disease, or loss comprising, administration of a nucleic acid sequence encoding Ascl1 and retinal reprogramming potentiating agents, including HDAC inhibitors, STAT-signaling inhibitors and microRNA manipulations in Ascl1-induced retinal regeneration.
Claims23
A nucleic acid molecule comprising a nucleic acid sequence encoding Ascl1 and a nucleic acid sequence encoding one or more reprogramming potentiators.
A method for inducing retinal regeneration in a subject comprising:
- a) administering to a retina of the subject a nucleic acid molecule comprising a nucleic acid sequence encoding Ascl1 and a nucleic acid sequence encoding one or more reprogramming potentiators, wherein Ascl1 induces neurogenesis from MG, and wherein the one or more reprogramming potentiators stimulate production of functional neurons from the Ascl1-induced MG.
(canceled)
A method for inducing retinal regeneration in a subject comprising:
- a) administering to a retina of the subject a polynucleotide sequence encoding Ascl1 (Achaete-scute-like family bHLH transcription factor 1), wherein expression of Ascl1 induces neurogenesis from Müller glia (MG);
- and b) sequentially or concurrently administering to the retina of the subject a combined therapy comprising a composition comprising one or more TSA/HDAC inhibitors (HDACi);
- and a composition comprising one or more Jak/STAT signaling pathway inhibitors (STATi), wherein the combined therapy stimulates production of functional neurons from the Ascl1-induced neurogenesis from the MG.
A nucleic acid molecule comprising a nucleic acid sequence encoding Ascl1 and a sequence selected from an MG-specific promoter sequence or a shRNA.
(canceled)
Dependencies are inferred from the claim text.