Treatment of erythropoietin deficiency in mice with systemically administered siRNA.

Querbes W, Bogorad RL, Moslehi J, Wong J, Chan AY, Bulgakova E, Kuchimanchi S, Akinc A, Fitzgerald K, Koteliansky V, Kaelin WG
Blood. 2012 120 (9): 1916-22

PMID: 22611156 · PMCID: PMC3433093 · DOI:10.1182/blood-2012-04-423715

Anemia linked to a relative deficiency of renal erythropoietin production is a significant cause of morbidity and medical expenditures in the developed world. Recombinant erythropoietin is expensive and has been linked to excess cardiovascular events. Moreover, some patients become refractory to erythropoietin because of increased production of factors such as hepcidin. During fetal life, the liver, rather than the kidney, is the major source of erythropoietin. In the present study, we show that it is feasible to reactivate hepatic erythropoietin production and suppress hepcidin levels using systemically delivered siRNAs targeting the EglN prolyl hydroxylases specifically in the liver, leading to improved RBC production in models of anemia caused by either renal insufficiency or chronic inflammation with enhanced hepcidin production.

MeSH Terms (23)

Anemia Animals Antimicrobial Cationic Peptides Base Sequence Cells, Cultured Erythropoiesis Erythropoietin Feasibility Studies Female Hepcidins Humans Hypoxia-Inducible Factor-Proline Dioxygenases Inflammation Liver Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Procollagen-Proline Dioxygenase Renal Insufficiency RNA, Small Interfering RNA Interference

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