Final report: Winn grant W11-035 Vapniarsky N, Lame M, McDonnel S and Murphy B. A lentiviral gene therapy strategy for the in vitro production of feline erythropoietin. PLoS ONE. 2012; 7: e45099. [free, full text] A common problem in domestic cats with chronic renal failure (CRF) is non-regenerative anemia. Currently, the administration of recombinant human erythropoietin (rHuEPO) frequently only improves anemia temporarily due to antibody development. Antibodies can develop within the first few months of rHuEPO administration. A clinically significant reaction has been reported in 20-70% of feline patients receiving rHuEPO. Adverse reactions reported with the use of rHUEPO in cats are refractory anemia, systemic hypertension, polycythemia, seizures, vomiting, iron deficiency, injection discomfort, cellulitis, cutaneous or mucocutaneous reactions, and arthralgia. Several therapeutic strategies utilizing species-specific recombinant EPO have attempted to address this issue of immunogenicity in cats.
In this study, the researchers wanted to investigate a possible gene delivery system for treatment of CRF-associated non-regenerative anemia that would have limited or no secondary immunogenicity, have stable and native transgene expression, and the ability to transduce both dividing and non-dividing cells. They looked at the ability of replication-incompetent lentiviral vectors to fulfill this list of requirements. They established an in vitro study system where feline erythropoietin cDNA was cloned from feline renal tissue and utilized in construction of a replication-defective lentiviral vector. The recombinant feline erythropoietin sequence was confirmed by subsequent sequencing. The results demonstrated the feasibility of this type of in vitro delivery system for the production of biologically active feline erythropoietin. In the future, cats with anemia due to CRF may benefit from a lentiviral gene therapy system. [VT]
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A common problem in domestic cats with chronic renal failure (CRF) is non-regenerative anemia. Currently, the administration of recombinant human erythropoietin (rHuEPO) frequently only improves anemia temporarily due to antibody development. Antibodies can develop within the first few months of rHuEPO administration. A clinically significant reaction has been reported in 20-70% of feline patients receiving rHuEPO. Adverse reactions reported with the use of rHUEPO in cats are refractory anemia, systemic hypertension, polycythemia, seizures, vomiting, iron deficiency, injection discomfort, cellulitis, cutaneous or mucocutaneous reactions, and arthralgia. Several therapeutic strategies utilizing species-specific recombinant EPO have attempted to address this issue of immunogenicity in cats.