Compositions useful in treatment of ornithine transcarbamylase (otc) deficiency
AssigneeThe Trustees of the University of Pennsylvania
InventorsLili Wang, James M. Wilson
Life of this patent
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Abstract
Viral vectors comprising engineered hOTC DNA and RNA sequences are provided which when delivered to a subject in need thereof are useful for treating hyperammonemia, ornithine transcarbamylase deficiency and symptoms associated therewith. Also provided are methods of using hOTC for treatment of liver fibrosis and/or cirrhosis in OTCD patients by administering hOTC.
Claims20
A composition comprising a nucleic acid sequence encoding human ornithine transcarbamylase (hOTCase) and expression control sequences which direct expression of hOTC in a liver cell, wherein the hOTC nucleic acid sequence is less than 80% identical to the wild-type hOTC sequence over the mature sequence or full length hOTC of SEQ ID NO:1, and expresses a functional hOTCase, wherein said hOTC nucleic acid sequence is selected from the nucleic acid sequence comprising SEQ ID NO:
- 5 or a nucleic acid sequence at least about 96 to about 99% identical thereto or a nucleic acid sequence selected from SEQ ID NO:
- 9, or a nucleic acid sequence at least about 96 to about 99% identical thereto.
A recombinant adeno-associated virus (rAAV) having an AAV capsid and packaged therein an expression cassette comprising at least one AAV inverted terminal repeat (ITR) sequence, an engineered nucleic acid sequence encoding human at least the mature ornithine transcarbamylase (hOTCase), and expression control sequences which direct expression of the hOTCase in a liver cell, said expression control sequences comprising a liver-specific promoter, wherein the hOTC nucleic acid sequence is less than 80% identical to the wild-type hOTC sequence over at least the mature hOTC of SEQ ID NO:
- 1 and comprises at least the mature hOTC of SEQ ID NO:
- 5 or a nucleic acid sequence at least about 96 to about 99.9% identical thereto or at least the mature hOTC of SEQ ID NO:
- 9 or a nucleic acid sequence at least about 96 to about 99.9% identical thereto.
A viral vector comprising a hOTC gene encoding a chimeric ornithine transcarbamylase which comprises at least mature human ornithine transcarbamylase with a heterologous transit sequence, wherein the coding sequence from the mature human ornithine transcarbamylase is selected from that of a nucleic acid sequence of SEQ ID NO:
- 3, 4, 5, 8 or 9.
Dependencies are inferred from the claim text.