23.02.1.3 Proteins that Provide a Novel Function or Activity

Erythropoietin (EPO) is probably best known for its use as a performance-enhancing drug used by cyclists to increase their red blood cells. With increased red blood cells, which carry oxygen, the cyclist has increased stamina in endurance events.

Physiologically, EPO is an endogenous glycoprotein produced by the kidney, and has a major role in promoting red blood cell survival and producing the precursors of red blood cells. Erythropoietin is an endogenous glycoprotein that stimulates red blood cell production. Recombinant DNA technology has allowed for the production of human erythropoietin homologues that vary in their carbohydrate groups but that are indistinguishable from human erythropoietin in biological activity and immunological reactivity. These include epoetin alfa (Procrit) and darbepoetin alfa (Aranesp) that are purified from Chinese hamster ovary cells into which the gene coding for human erythropoietin has been inserted. These drugs are indicated for the treatment of anaemia associated with chronic renal failure (CRF) and for other condition where there is a reduced number of red blood cells e.g. as a result of the treatment of cancer.

Similarly, tenecteplase (Metalyse) is a tissue plasminogen activator (tPA) produced by recombinant DNA technology that binds to the fibrin component of the thrombus (blood clot) and converts thrombus-bound plasminogen to plasmin, which degrades the fibrin matrix of the thrombus. Tenecteplase has a higher fibrin specificity and greater resistance to inactivation by its endogenous inhibitor compared to native tPA. Metalyse is indicated for the thrombolytic treatment of the acute phase of myocardial infarction.

Introduction of a foreign substance (an antigen) into a vertebrate such as a mouse or a human has a profound effect on the body’s defence mechanism, the immune system. One response to such an exposure is that some of the immune system's B-cells will turn into plasma cells and start to produce antibodies (immunoglobulins) that bind to that antigen. Indeed the word antigen is derived from the term antibody generator. Although each activated B-cell is only capable of producing one kind of antibody, antigen exposure results in the activation of different B-cells that each produce structurally different antibodies that bind to different parts (epitopes) of the antigen. This natural mixture of antibodies is known as polyclonal antibodies. These circulating antibodies protect their host by binding to and neutralising foreign proteins (e.g. toxins) resulting in negation of their deleterious effects.