Tissues or organs for use in xenotransplantation
OwnerMonika Liljedahl, Daniela Marcantonio +1inventors
InventorsMonika Liljedahl, Daniela Marcantonio, Simon Eric Aspland
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Abstract
The present invention provides cells, tissues or organs for use in cell therapy or xenotransplantation in which at least one gene comprising an antigenic determinant recognized by a recipient organism has been disrupted. The present invention also includes methods of administering such cells and transplanting such tissues or organs in which genes encoding antigenic determinants recognized by the recipient organism have been disrupted.
Claims73
A genetically engineered cell in which a gene encoding an enzyme has been disrupted, wherein said gene encodes an enzyme selected from the group consisting of a Forssman glycolipid synthetase and a PK enzyme, wherein said PK enzyme is an enzyme associated with the synthesis of a PK carbohydrate.
A genetically engineered cell in which a gene comprising the sequence selected from the group consisting of SEQ ID NO:
- 29 and SEQ ID NO:
- 39 has been disrupted.
A recombinant nucleic acid comprising:
- a 5′ region homologous to a portion of a gene responsible for the production of an antigenic determinant, wherein said gene is selected from the group consisting of a Forssman glycolipid synthetase and a PK enzyme;
- a 3′ region homologous to a portion of said gene;
- and
- a nucleotide sequence which prevents the synthesis of the Forssman glycolipid synthetase or the PK enzyme, said nucleotide sequence being disposed between said 5′ region and said 3′ region.
A method of disrupting a gene comprising a sequence selected from the group consisting of SEQ ID NO:
- 29 and SEQ ID NO:
- 39, comprising:
- introducing a nucleic acid comprising a sequence homologous to at least a portion of the coding region of said gene into a cell, wherein said homologous sequence comprises a disruption in said coding region which prevents said cell from expressing the full length polypeptide normally encoded by said coding region;
- and
- replacing at least one chromosomal copy of said gene with said homologous sequence comprising said disruption in said coding region.
An isolated nucleic acid sequence comprising the sequence of SEQ ID NO:
- 29.
An isolated nucleic acid sequence comprising a nucleic acid sequence selected from the group consisting of a nucleic acid sequence comprising a sequence having at least 99% identity to the sequence of SEQ ID NO:
- 29, a nucleic acid sequence comprising a sequence having at least 97% identity to the sequence of SEQ ID NO:
- 29, a nucleic acid sequence comprising a sequence having at least 95% identity to the sequence of SEQ ID NO:
- 29, and a nucleic acid sequence comprising a sequence having at least 99% identity to the sequence of SEQ ID NO:
- 29, wherein nucleotide sequence identity is determined using BLASTN version 2.0 with the default parameters.
An isolated nucleic acid sequence comprising a sequence comprising at least 600, 700, 800, 900 or 1000 consecutive nucleotides of the sequence set forth in SEQ ID NO:
- 29.
An isolated nucleic acid encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:
- 30.
An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO:
- 30.
An isolated nucleic acid sequence comprising the sequence of SEQ ID NO:
- 39.
An isolated nucleic acid sequence comprising a nucleic acid sequence selected from the group consisting of a nucleic acid sequence comprising a sequence having at least 99% identity to the sequence of SEQ ID NO:
- 39, a nucleic acid sequence comprising a sequence having at least 97% identity to the sequence of SEQ ID NO:
- 39, a nucleic acid sequence comprising a sequence having at least 95% identity to the sequence of SEQ ID NO:
- 39, and a nucleic acid sequence comprising a sequence having at least 90% identity to the sequence of SEQ ID NO:
- 39, wherein nucleotide sequence identity is determined using BLASTN version 2.0 with the default parameters.
An isolated nucleic acid sequence comprising a sequence comprising at least 600, 700, 800, 900 or 1000 consecutive nucleotides of the sequence set forth in SEQ ID NO:
- 39.
An isolated nucleic acid encoding a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:
- 40.
An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO:
- 40.
Dependencies are inferred from the claim text.