Granted Patent
B2
US 12,473,545 · App. 17/826,224 · Granted Nov 18, 2025
Regulation of RAN translation by PKR and eIF2α-P pathways
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Abstract
Methods and compositions for modulating repeat non-ATG protein (RAN protein) translation are provided. In some aspects, the disclosure provides methods of inhibiting RAN protein translation by contacting a cell with an effective amount of an inhibitor of eIF2 phosphorylation or an inhibitor of protein kinase R (PKR). In some embodiments, methods described by the disclosure are useful for treating diseases associated with RAN protein translation, such as certain neurodegenerative diseases.
Claims (8)
1 . A recombinant adeno-associated virus (rAAV) comprising:
(i) a capsid protein; and
(ii) a nucleic acid comprising a transgene operably linked to a promoter, wherein the transgene encodes a dominant negative variant of protein kinase R (PKR) comprising a K296R mutation relative to amino acid position 296 in the wild-type PKR amino acid sequence set forth in SEQ ID NO: 15.
2 . The rAAV of claim 1 , wherein the capsid protein is an AAV9 capsid protein, or a variant thereof.
3 . The rAAV of claim 1 , wherein the nucleic acid further comprises at least one inverted terminal repeat (ITR).
4 . The rAAV of claim 1 , wherein the rAAV is formulated for delivery by injection.
5 . A pharmaceutical composition comprising the rAAV of claim 1 and a pharmaceutically acceptable excipient.
6 . The rAAV of claim 3 , wherein the ITR is an AAV2 ITR.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 24, 2022
From: RANUM, LAURA; ZU, TAO
To: UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INCORPORATED
Reel/Frame 060887/0856 →
Continuity (4)
Continuation
16605992
Provisional Application
62563588
· Sep 26, 2017
Provisional Application
62486424
· Apr 17, 2017
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