Correction of anemia in uremic rats by intramuscular injection of lentivirus carrying an erythropoietin gene

Keun Oh Tae, Hong Quan Gui, Young Kim Hae, Frank Park, Taik Kim Seung

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Anemia is an inevitable consequence of chronic renal failure. Gene therapy using lentiviral vector (LV) would be an effective tool to treat anemia associated with renal failure. Methods: A LV carrying the erythropoietin (EPO) cDNA was administered to skeletal muscle of partially nephrectomized rats, which is a model of uremia. The red blood cell production and serum EPO levels were temporally monitored in these rats. Polymerase chain reaction assays were done to validate the presence of the LV in the experimental rats. Results: After a single intramuscular injection of LV at a dose of 55 μg p24 Gag antigen (∼5 × 107 transducing units), blood hematocrit (Hct) levels increased and peaked at 3 weeks (47.8 ± 4.2%, p < 0.01, n = 8) with the levels being maintained for at least 20 weeks (duration of study; 44.9 ± 3.3%, p < 0.01, n = 3). The control rats receiving LV expressing lacZ had Hct levels of 36.9 ± 4.1% (n = 8) at 3 weeks and 33.1 ± 3.7% (n = 4) at 20 weeks, respectively. The serum EPO levels in the rats injected with the LV expression EPO significantly increased (p < 0.01)to 156.3 ± 3.0 mU/ ml compared to the control rats (63.9 ± 1.7 mU/ml). Polymerase chain reaction analysis of the isolated genomic DNA from the LV-injected rats showed specific positive detection of the LV in only the skeletal muscle tissue at the site of injection, whereas the other tissues, including the liver, spleen, and kidney, were negative. Conclusions: This study demonstrates that intramuscular injection of LV can produce highly efficient and sustained EPO secretion in uremic rats, and suggests that this approach could be an effective tool to deliver secretable proteins at therapeutic levels in various animal disease models.

Original languageEnglish (US)
Pages (from-to)326-334
Number of pages9
JournalAmerican Journal of Nephrology
Volume26
Issue number4
DOIs
StatePublished - Sep 1 2006
Externally publishedYes

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Lentivirus
Intramuscular Injections
Erythropoietin
Anemia
Genes
Hematocrit
Skeletal Muscle
gag Gene Products
Animal Disease Models
Polymerase Chain Reaction
Uremia
Serum
Genetic Therapy
Chronic Kidney Failure
Renal Insufficiency
Spleen
Complementary DNA
Erythrocytes
Kidney
Muscles

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Correction of anemia in uremic rats by intramuscular injection of lentivirus carrying an erythropoietin gene. / Tae, Keun Oh; Gui, Hong Quan; Hae, Young Kim; Park, Frank; Seung, Taik Kim.

In: American Journal of Nephrology, Vol. 26, No. 4, 01.09.2006, p. 326-334.

Research output: Contribution to journalArticle

Tae, Keun Oh ; Gui, Hong Quan ; Hae, Young Kim ; Park, Frank ; Seung, Taik Kim. / Correction of anemia in uremic rats by intramuscular injection of lentivirus carrying an erythropoietin gene. In: American Journal of Nephrology. 2006 ; Vol. 26, No. 4. pp. 326-334.
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abstract = "Background: Anemia is an inevitable consequence of chronic renal failure. Gene therapy using lentiviral vector (LV) would be an effective tool to treat anemia associated with renal failure. Methods: A LV carrying the erythropoietin (EPO) cDNA was administered to skeletal muscle of partially nephrectomized rats, which is a model of uremia. The red blood cell production and serum EPO levels were temporally monitored in these rats. Polymerase chain reaction assays were done to validate the presence of the LV in the experimental rats. Results: After a single intramuscular injection of LV at a dose of 55 μg p24 Gag antigen (∼5 × 107 transducing units), blood hematocrit (Hct) levels increased and peaked at 3 weeks (47.8 ± 4.2{\%}, p < 0.01, n = 8) with the levels being maintained for at least 20 weeks (duration of study; 44.9 ± 3.3{\%}, p < 0.01, n = 3). The control rats receiving LV expressing lacZ had Hct levels of 36.9 ± 4.1{\%} (n = 8) at 3 weeks and 33.1 ± 3.7{\%} (n = 4) at 20 weeks, respectively. The serum EPO levels in the rats injected with the LV expression EPO significantly increased (p < 0.01)to 156.3 ± 3.0 mU/ ml compared to the control rats (63.9 ± 1.7 mU/ml). Polymerase chain reaction analysis of the isolated genomic DNA from the LV-injected rats showed specific positive detection of the LV in only the skeletal muscle tissue at the site of injection, whereas the other tissues, including the liver, spleen, and kidney, were negative. Conclusions: This study demonstrates that intramuscular injection of LV can produce highly efficient and sustained EPO secretion in uremic rats, and suggests that this approach could be an effective tool to deliver secretable proteins at therapeutic levels in various animal disease models.",
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AU - Tae, Keun Oh

AU - Gui, Hong Quan

AU - Hae, Young Kim

AU - Park, Frank

AU - Seung, Taik Kim

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N2 - Background: Anemia is an inevitable consequence of chronic renal failure. Gene therapy using lentiviral vector (LV) would be an effective tool to treat anemia associated with renal failure. Methods: A LV carrying the erythropoietin (EPO) cDNA was administered to skeletal muscle of partially nephrectomized rats, which is a model of uremia. The red blood cell production and serum EPO levels were temporally monitored in these rats. Polymerase chain reaction assays were done to validate the presence of the LV in the experimental rats. Results: After a single intramuscular injection of LV at a dose of 55 μg p24 Gag antigen (∼5 × 107 transducing units), blood hematocrit (Hct) levels increased and peaked at 3 weeks (47.8 ± 4.2%, p < 0.01, n = 8) with the levels being maintained for at least 20 weeks (duration of study; 44.9 ± 3.3%, p < 0.01, n = 3). The control rats receiving LV expressing lacZ had Hct levels of 36.9 ± 4.1% (n = 8) at 3 weeks and 33.1 ± 3.7% (n = 4) at 20 weeks, respectively. The serum EPO levels in the rats injected with the LV expression EPO significantly increased (p < 0.01)to 156.3 ± 3.0 mU/ ml compared to the control rats (63.9 ± 1.7 mU/ml). Polymerase chain reaction analysis of the isolated genomic DNA from the LV-injected rats showed specific positive detection of the LV in only the skeletal muscle tissue at the site of injection, whereas the other tissues, including the liver, spleen, and kidney, were negative. Conclusions: This study demonstrates that intramuscular injection of LV can produce highly efficient and sustained EPO secretion in uremic rats, and suggests that this approach could be an effective tool to deliver secretable proteins at therapeutic levels in various animal disease models.

AB - Background: Anemia is an inevitable consequence of chronic renal failure. Gene therapy using lentiviral vector (LV) would be an effective tool to treat anemia associated with renal failure. Methods: A LV carrying the erythropoietin (EPO) cDNA was administered to skeletal muscle of partially nephrectomized rats, which is a model of uremia. The red blood cell production and serum EPO levels were temporally monitored in these rats. Polymerase chain reaction assays were done to validate the presence of the LV in the experimental rats. Results: After a single intramuscular injection of LV at a dose of 55 μg p24 Gag antigen (∼5 × 107 transducing units), blood hematocrit (Hct) levels increased and peaked at 3 weeks (47.8 ± 4.2%, p < 0.01, n = 8) with the levels being maintained for at least 20 weeks (duration of study; 44.9 ± 3.3%, p < 0.01, n = 3). The control rats receiving LV expressing lacZ had Hct levels of 36.9 ± 4.1% (n = 8) at 3 weeks and 33.1 ± 3.7% (n = 4) at 20 weeks, respectively. The serum EPO levels in the rats injected with the LV expression EPO significantly increased (p < 0.01)to 156.3 ± 3.0 mU/ ml compared to the control rats (63.9 ± 1.7 mU/ml). Polymerase chain reaction analysis of the isolated genomic DNA from the LV-injected rats showed specific positive detection of the LV in only the skeletal muscle tissue at the site of injection, whereas the other tissues, including the liver, spleen, and kidney, were negative. Conclusions: This study demonstrates that intramuscular injection of LV can produce highly efficient and sustained EPO secretion in uremic rats, and suggests that this approach could be an effective tool to deliver secretable proteins at therapeutic levels in various animal disease models.

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