Reagents for treatment of oculopharyngeal muscular dystrophy (OPMD) and use thereof
AssigneeBenitec IP Holdings Inc.
InventorsVanessa Strings-Ufombah, David Suhy
Life of this patent
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Abstract
The present disclosure relates to RNA interference (RNAi) reagents, such as short hairpin microRNA (shmiR) and short hairpin RNA (shRNA), for treatment of oculopharyngeal muscular dystrophy (OPMD), compositions comprising same, and use thereof to treat individuals suffering from OPMD or which are predisposed thereto. The present disclosure also relates to the use of the RNAi reagents in combination with PABPN1 replacement reagents, such as constructs which encode functional PABPN1 protein, for treatment of OPMD, compositions comprising same, and use thereof to treat individuals suffering from OPMD or which are predisposed thereto.
Claims27
A nucleic acid comprising a DNA sequence which encodes a short hairpin micro-RNA (shmiR) targeting a transcript of PABPN1, said shmiR comprising:
- an effector sequence of at least 17 nucleotides in length;
- an effector complement sequence;
- a stemloop sequence;
- and
- a primary micro RNA (pri-miRNA) backbone;
- wherein the effector sequence is complementary to a region of corresponding length in an RNA transcript set forth in SEQ ID NO:
- 13 or complementary to a region of corresponding length in an RNA transcript set forth in SEQ ID NO:
- 13 with the exception of 1, 2, 3 or 4 base mismatches relative to the RNA transcript set forth in SEQ ID NO:
- 13.
An adeno-associated virus (AAV) comprising a DNA construct comprising:
- (a) a muscle-specific promoter;
- (b) a ddRNAi construct comprising:
- a nucleic acid comprising a DNA sequence encoding a shmiR comprising an effector sequence set forth in SEQ ID NO:
- 39 and an effector complement sequence set forth in SEQ ID NO:
- 38;
- and a nucleic acid comprising a DNA sequence encoding a shmiR comprising an effector sequence set forth in SEQ ID NO:
- 31 and an effector complement sequence set forth in SEQ ID NO:
- 30;
- and
- (c) a PABPN1 construct comprising a DNA sequence encoding a functional PABPN1 protein having a mRNA transcript which is not targeted by the shmiRs encoded by the ddRNAi construct.
Dependencies are inferred from the claim text.