Expression of erythropoietin in cats treated with a recombinant adeno-associated viral vector.
OBJECTIVE
To characterize the biological effects of IM administration of a recombinant adeno-associated virus serotype 2 (rAAV2) vector containing feline erythropoietin (fEPO) cDNA and determine whether readministration of the vector or removal of muscle tissue at the injection sites alters those effects.


METHODS
10 healthy 7-week-old specific pathogen-free cats.


METHODS
Cats received 1 X 10(7) infective units (iU; n = 3), 1 X 10(8) iU (3), or 1 X 10(9) iU (2) of rAAV2-fEPO vector IM (day 0). Two control cats received an rAAV2 vector containing the LacZ gene (1 X 10(9) iU, IM). In all cats, hematologic variables and serum fEPO concentration were measured at intervals; anti-rAAV2 antibody titer was measured on day 227. In cats that did not respond to treatment, the rAAV2-fEPO vector was readministered. Injection sites were subsequently surgically removed.


RESULTS
Compared with control cats, cats treated with 1 X 10(9) iU of rAAV2-fEPO vector had increased Hct and serum fEPO concentrations. One of these cats developed pure RBC aplasia; its Hct normalized following injection site excision. Cats receiving lower doses of vector had no response; on retreatment, 1 of those cats developed sustained erythrocytosis that persisted despite injection site removal and the others did not respond or responded transiently. Antibodies against rAAV2 were detected in all vector-treated cats.


CONCLUSIONS
Gene therapy may be an effective treatment for cats with hypoproliferative anemia. However, rAAV2-fEPO vector administration may result in pure RBC aplasia or pathologic erythrocytosis, and injection site removal does not consistently abolish the biological response.
Walker
Mark C
MC
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA.
Mandell
Tamara C
TC
Crawford
P Cynda
PC
Simon
Greg G
GG
Cahill
Kevin S
KS
Fernandes
Peter J
PJ
MacLeod
James N
JN
Byrne
Barry J
BJ
Levy
Julie K
JK
D000199:Actins / Q000235:genetics; D000740:Anemia / Q000628:therapy / Q000662:veterinary*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002371:Cat Diseases / Q000628:therapy*; D002415:Cats; D018076:DNA, Complementary / Q000235:genetics; D000229:Dependovirus; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D004921:Erythropoietin / Q000097:blood* / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism*; D009500:Neutralization Tests / Q000662:veterinary; D011401:Promoter Regions, Genetic / Q000235:genetics
D000199:Actins; D000914:Antibodies, Viral; D018076:DNA, Complementary; D004921:Erythropoietin