AAV vectors produced by insect cells comprising Rep52 and Rep78 coding sequences with differential codon biases

A recombinant adeno-associated virus (rAAV) virion obtainable by culturing an insect cell under conditions such that rAAV virions are produced and recovering the rAAV virions, wherein the insect cell comprises a baculoviral vector comprising:

• (i) a first nucleotide sequence encoding a first amino acid sequence of an AAV Rep52 protein selected from the group consisting of:
• (a) a sequence of at least 85% identity with SEQ ID NO:
• 10;
• (b) a nucleotide sequence complementary to the full length sequence of (a);
• and
• (c) a nucleotide sequence that differs from the sequence of (a) due to degeneracy of the genetic code;
• and
• (ii) a second nucleotide sequence encoding a second amino acid sequence of an AAV Rep78 protein;
• (iii) a third nucleotide sequence comprising two AAV inverted terminal repeat (ITR) sequences and a nucleotide sequence encoding a gene product located between the two AAV ITR sequences, wherein the gene product, when expressed in a target cell, provides ablation of an undesired activity or complementation of a genetic defect;
• and,
• (iv) a fourth nucleotide sequence comprising AAV capsid protein-coding sequences operably linked to expression control sequences for expression in an insect cell;
• wherein the first and the second amino acid sequences share at least 90% sequence identity in a region from the second amino acid residue to the C-terminal residue of the AAV Rep52 protein, and
• wherein a portion of the first nucleotide sequence and a portion of the second nucleotide sequence that encode the region from the second amino acid residue to the C-terminal residue of the AAV Rep52 protein each comprise one or more contiguous stretches of at least 300 nucleotides that are less than 90% identical.