The Haemopoietic Activity and Pharmacokinetics of EPO-Fc, EPO-Fcneo and Alb-EPO Fused Proteins, Derivatives of Human Erythropoietin

Автор: N.A. Gavrilova, A.M. Cheremnykh, R.A. Bobreneva, E.V. Askerova, T.I. Kalinina, N.V. Bulushova, G.G. Chestukhina, and V.L. Yurin

Страница: 38-49

The Haemopoietic Activity and Pharmacokinetics of EPO-Fc, EPO-Fcneo and Alb-EPO Fused Proteins, Derivatives of Human Erythropoietin

Biotekhnologiya, 2012, N 5, P. 38-49

UDC 602.6.615.373.602.6:612

Section:  “Producers, Biology, Selection, and Gene Engineering”

N.A. Gavrilova ^*,  A.M. Cheremnykh,  R.A. Bobreneva,  E.V. Askerova,  T.I. Kalinina,  N.V. Bulushova,  G.G. Chestukhina,  and  V.L. Yurin ^*

The State Research Institute for Genetics and Selection of Industrial Microorganisms,  117545, Moscow Russia

e-mail:  gavrilova.07@mail.ru,  yurin@genetika.ru

Genetic constructs for erythropoietin (EPO) and the modified Fc fragments of IgG1 (EPO-Fc and EPO-Fcneo) and albumin (Alb-linker-EPO) as representatives of long-living human blood proteins have been designed. Cell lines on the basis of CHO producing the above proteins were obtained using the Flp/FRT-dependant site-specific transgene integration in the DG44(FRT+/Dhfr+) genome of the recipient CHO cells. The biochemical, biological and pharmacokinetic properties of the EPO-Fc, EPO-Fcneo and Alb-EPO proteins were assessed. It was established that the above proteins possess the twofold enhanced specific hemopoietic activity on average, 4—5-fold lower rate of elimination and 2—2,5-fold longer serum half-life in murine organism, as compared to the unmodified EPO(BRP) standard. The fused proteins provide a stable and long-time increase (by 10—12%) in the level of hemoglobin in test animals' blood. A long-term biological activity of the fused proteins ensured by their longer circulation in blood was shown.

Key words:  biological activity,  erythropoietin,  expression,  genetic constructs,  mammalian cells,  pharmacokinetic.

The full English version of the article was published in “Biotechnology in Russia”, 2012, Issue 5, pp. 38-49 as N.A. Gavrilova, A.M. Cheremnykh, R.A. Bobreneva, E.V. Askerova, T.I. Kalinina, N.V. Bulushova, G.G. Chestikhina, V.L. Yurin “Haemopoetic Activity and Pharmacokinetics of EPO-Fc, EPO-Fcneo and Alb-EPO Fused Proteins, Derivatives of Human Erythropoietin”.

It is contained at the Russian Scientific Electron Library website:  http://elibrary.ru/item.asp?id=21532470

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