Robust factor IX minigene expression cassette (TTR)

Researchers in Dr. Mark Kay's laboratory at Stanford University have designed a new liver-specific expression cassette for inserting genes into double-stranded AAV (adeno-associated virus) vectors for gene therapy. AAV vectors are useful for gene therapy because they can be used to transduce different types of dividing and non-dividing cells of different tissues. They can establish stable, long-term transgene expression without the toxicity or human diseases associated with other viral vectors. It is believed that double-stranded AAV vectors are 10 - 100 times more robust than single stranded AAV vectors and would therefore require much smaller doses than single-stranded AAV to produce a therapeutic effect. However, a limited amount of exogenous DNA can be inserted into the double-stranded vectors. Now, Stanford inventors have linked a synthetic liver-specific enhancer to a mini promoter to generate a Factor IX vector that can be packaged into double-stranded AAV vector. This cassette was used to express Factor IX in vivo.

Stage of Research:
The inventors have used the expression cassette with double stranded AAV vectors for Factor IX gene therapy in mice.