Tissue preferential codon modified expression cassettes, vectors containing same, and uses thereof
AssigneeThe Trustees of the University of Pennsylvania
InventorsJames M. Wilson, Anna Tretiakova
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Abstract
Described herein are synonymously altered gene sequences which express protein in differing levels within secretory as compared to non-secretory target tissue. An expression cassette comprising an open reading frame (ORF) for a protein under the control of regulatory sequences which direct expression of the product in cell, which ORF has been modified to preferentially increase expression levels in a selected tissue, wherein the modified ORF is characterized by a triplet frequency of any one of Tables 3-12, 16 or 17.
Claims22
A method for improving expression of a selected gene product in a selected type of target tissue within a selected species, said method comprising:
- constructing an expression cassette comprising a coding sequence for a selected gene product generated with a selected codon frequency of Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, Table 10, Table 11, Table 12, Table 16, or Table 17.
An expression cassette comprising an open reading frame (ORF) for an antibody construct under the control of regulatory sequences which direct expression of the product in a cell, which ORF has been modified to preferentially increase expression levels in target tissue cells, wherein the modified ORF is characterized by a triplet frequency of any one of Tables 3 to 12.
An expression cassette comprising an open reading frame (ORF) for an antibody construct under the control of regulatory sequences which direct expression of the product in cell, which ORF has been modified to preferentially increase expression levels in non-secretory cells, wherein the modified ORF is characterized by a triplet frequency of Table 16 or Table 17.
An expression cassette comprising an open reading frame (ORF) for an antibody construct under the control of regulatory sequences which direct expression of the product in a muscle cell, which ORF has been modified to preferentially increase expression levels in muscle, wherein the modified ORF has a sequence selected from:
- ORF1 having a sequence of SEQ ID NO:
- 9, ORF 2 having a sequence of SEQ ID NO:
- 8, ORF11 having a sequence of SEQ ID NO:
- 7, ORF26 having a sequence of SEQ ID NO:
- 6, ORF 28 having a sequence of SEQ ID NO:
- 5, ORF 30 having a sequence of SEQ ID NO:
- 4, ORF35 having a sequence of SEQ ID NO:
- 3, ORF39 having a sequence of SEQ ID NO:
- 2, ORF40 having a sequence of SEQ ID NO:
- 1, ORF42 having a sequence of SEQ ID NO:
- 30, IA having a sequence of SEQ ID NO:
- 10, or IAM having a sequence of SEQ ID NO:
- 11.
A recombinant AAV comprising an AAV8 capsid and an expression cassette for an anti-HIV antibody, wherein the expression cassette is adapted for expression in a selected target tissue, said expression cassette comprising a modified ORF having a sequence selected from the group consisting of ORF1 having a sequence of SEQ ID NO:
- 9, ORF 2 having a sequence of SEQ ID NO:
- 8, ORF11 having a sequence of SEQ ID NO:
- 7, ORF26 having a sequence of SEQ ID NO:
- 6, ORF 28 having a sequence of SEQ ID NO:
- 5, ORF 30 having a sequence of SEQ ID NO:
- 4, ORF35 having a sequence of SEQ ID NO:
- 3, ORF39 having a sequence of SEQ ID NO:
- 2, ORF40 having a sequence of SEQ ID NO:
- 1, ORF42 having a sequence of SEQ ID NO:
- 30, IA having a sequence of SEQ ID NO:
- 10, and IAM having a sequence of SEQ ID NO:
- 11.
Dependencies are inferred from the claim text.