Chiorini, John (Jay) (NHLBI)
The invention described and claimed in this patent application provides for novel vectors and viral particles which comprise adeno-associated virus serotype 5 (AAV5). AAV5 is a single-stranded DNA virus of either plus or minus polarity which, like other AAV serotypes (e.g., AAV4, AAV2) requires a helper virus for replication. AAV type 2 has the interesting and potentially useful ability to integrate into human chromosome 19 q 13.3-q ter. This activity is dependent on the non-structural, Rep, proteins of AAV2. The Rep proteins of AAV types 2 and 5 are dissimilar and are not able to substitute in DNA replication of the heterologous serotype.
AAV5 offers several advantages which make it attractive for use in gene therapy: 1. increased production (10-50 fold greater than AAV2); 2. distinct integration locus when compared to AAV2; 3. Rep protein and ITR regions do not complement other AAV serotypes; and 4. appears to utilize different cell surface attachment molecules than those of AAV type 2.