Expression of erythropoietin in cats treated with a recombinant adeno-associated viral vector

Abstract

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.

Intramuscular IL-12 Electrogene Therapy for Treatment of Spontaneous Canine Tumors

“…muscle dystrophies), intravascular release of therapeutic proteins resulting in expansion of this therapy on systemic level (e.g.immunomodulation) and DNA vaccination against tumor antigens or infectious agents. Intramuscular gene therapy in veterinary medicine has already been successfully applied for a variety of indications in a number of different animal species, for example in cattle and sheep (Howell et al, 2008;Mena et al, 2001;Tollefsen et al, 2003), horses , pigs (Brown et al, 2004;Gravier et al, 2007) as well as cats (Brown et al, 2009;Ross et al, 2006;Walker et al, 2005) and dogs. In dogs mainly ex vivo delivery approach and viral vectors have been used in different disease models, primarily for treatment of hemophilia B, muscle dystrophies and in therapy of ischemic heart disease Banks & Chamberlain, 2008;Dixon & Spinale, 2009;Hasbrouck & High, 2008;Haurigot et al, 2010;Herzog et al, 2001;Katz et al, 2010;Ohshima et al, 2009;L.…”

A Lentiviral Gene Therapy Strategy for the In Vitro Production of Feline Erythropoietin

“…A rAAV-rfEPO vector, when administered intramuscularly to normal healthy cats, resulted in an increase in hematocrit over a 7 week period [16]. In a subsequent study, healthy cats treated with the lower-end vector dose had variable to no response while cats treated with the higher dose had significantly increased hematocrits during the first 3 weeks of rfEPO treatment [2]. Antibodies against the recombinant adeno-associated vector were detected in all of the vector treated cats.…”

“…The glycoprotein hormone erythropoietin, made by the peritubular cells of the renal cortex [1], [2], [3], stimulates the production of red blood cells. Erythropoietin-responsive anemia is a common cause of morbidity in cats affecting 32–65% of cats with chronic renal failure (CRF) [4], [5], [6].…”

“…Adeno-associated viral vectors expressing recombinant feline erythropoietin (rAAV-rfEPO) have been developed [2], [16]. A rAAV-rfEPO vector, when administered intramuscularly to normal healthy cats, resulted in an increase in hematocrit over a 7 week period [16].…”

“…In the same study, one cat developed RCA and another developed pathologic erythrocytosis. The authors speculated that posttranslational differences may exist between the endogenous and rfEPO synthesis intramuscularly [2]. Nevertheless, the genetic code of the rfEPO cDNA utilized in the construction of this viral vector encoded glycine (44 GGG ) in lieu of glutamic acid (44 GAG ) [2].…”