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Blood, Vol. 92 No. 5 (September 1), 1998:
pp. 1512-1517
RAPID COMMUNICATION
Control of Erythropoietin Delivery by Doxycycline in Mice After
Intramuscular Injection of Adeno-Associated Vector
Delphine Bohl,
Anna Salvetti,
Philippe Moullier, and
Jean Michel Heard
From Laboratoire Rétrovirus et Transfert Génétique,
CNRS URA 1157, Institut Pasteur, Paris; and Laboratoire de
Thérapie Génique, CHU-Hôtel-Dieu, Nantes, France.
We reported previously that controlled expression of a foreign gene
in response to tetracycline derivative can be accomplished in mice by
the autologous transplantation of retrovirus-modified muscle cells.
Although regulated systemic delivery of therapeutic proteins from
engineered tissues has potential clinical application, the
transplantation of muscle cells is not currently feasible in humans.
Several studies have shown that a single injection of adeno-associated
virus (AAV) vectors into mouse muscle results in long-term expression
of reporter genes as well as sustained delivery of proteins into the
serum. Because this method is potentially applicable clinically, we
constructed an AAV vector in which the expression of the mouse
erythropoietin (Epo) cDNA is modulated in response to doxycycline. The
vector was injected intramuscularly in normal mice. We observed that
hematocrit and serum Epo concentrations could be modulated over a
29-week period in response to the presence or absence of doxycycline in
the drinking water of these animals. Thus, a regulated gene expression
cassette can be incorporated into a single AAV vector, such that
intramuscular injection of the vector allows sustained and regulated
expression of a desired gene.
© 1998 by The American Society of Hematology.
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