Ditto--very nice report, hope you have
not given up too many shares on the way
up. Since you seem to have the hot hand,
let us know what your next homework
assignment turns up.
I did a query to see how their vector might
be designed, this might be an older version,
but interesting to compare theirs with others'
constructs, if only to learn some of the jargon--
if anybody has a more recent scientific paper in
front of them, maybe they could post some snips
from the materials and methods section.
Like I said, this is older, and was with mice, but
might be interesting background, if not already
somewhere on this thread. Also check out the Rabinowitz
and Samulski review article on AAV at Current Opinion,
the url is on the Gene therapy thread, a search here
on SI should turn it up.
LONG-TERM EXPRESSION OF HUMAN COAGULATION FACTOR IX FOLLOWING ADMINISTRATION OF AAV VECTORS TO MOUSE MUSCLE AND LIVER.
Hiroyuki Nakai*, Greg M. Podsakoff*, Peter C. Colosi*, R.C. Eisensmith#,Gary J. Kurtzman*, Linda B. Couto*
* Avigen, Inc. 1201 Harbor Bay Parkway, Alameda, Ca. 94502;
# Mount Sinai Medical School, One Gustave L. Levy Place, New York,
N.Y. 10029-6574.
Recombinant adeno-associated virus (AAV) vectors are potential
vehicles for transferring therapeutic genes into both dividing and
nondividing cells. We have investigated the feasibility of using AAV
vectors for the treatment of hemophilia B and demonstrated efficient
long-term expression of circulating human factor IX (hFIX) following a single administration of AAV-hFIX to either muscle or liver when the gene is controlled by an appropriate regulatory element. We constructed two AAV-hFIX vectors, AAV-CMV-hFIX and AAV-EF1a-hFIX, containing the CMV-IE enhancer/promoter and the human polypeptide chain elongation factor 1a promoter, respectively. Nude mice (NCr nu/nu) that received 1.8x10 (superscript)12 particles of AAV-CMV-hFIX intra- muscularly produced detectable levels of circulating hFIX two week post-injection. A peak of 270 ng/ml hFIX/ml was observed 4 months post injection and levels of 100-150 ng/ml have persisted for at least 8 months. Following direct injection of AAV-EF1a-hFIX into the livers of nude mice, sustained hFIX levels of about 200 ng/ml were observed for up to 5 months. In contrast, AAV-CMV-hFIX or AAV-EF1a-hFIX delivered to the liver or muscle, respectively, produced very low or no detectable levels of hFIX. Thus, AAV-mediated gene transfer toward the muscle or liver provides a feasible strategy for gene therapy of hemophilia B, however the choice of an appropriate promoter in targeting tissue is essential.
query
google.com
turned up this
med.unc.edu
If you want to compare vectors for fun, try reading
PNAS Vol 96, pp. 8657-8662...this paper is one which
delivered hGH to mice--sorry, no humans, but worth a
read. I'll write Avigen and try and get their PNAS
paper. |
