Engineered tissue plasminogen activator

CH12 RECOMBINANT BLOOD PRODUCTS AND THERAPEUTIC ENZYMES 

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Along with the production of insulin, many other medical uses have been achieved for recombinant DNA. This includes the production of erythropoetin, a hormone used to stimulate production of red blood cells in anemic people tissue plasminogen activator, an enzyme that dissolves blood clots in heart attack victims and antihemophilic human factor VIII, used to prevent and control bleeding for hemophiliacs. These three important genetically engineered proteins were all cloned in hamster cell cultures. 

While some potential therapeutic proteins can be isolated and purihed from natural sources, it may be impractical to extract a sufficient amount for therapeutic purposes. This is the case for tissue plasminogen activator (tPA). While its therapeutic potential was quickly recognized, the protein was present naturally in such small amount that it was not possible to obtain quantities sufficient for chnical evaluation. Advances in biotechnology, including the development of recombinant DNA engineering, permitted production of recombinant tPA in sufficient quantities to evaluate its effects on occluded coronary arteries and to eventually develop a product. 

Second-generation tissue plasminogen activator (tPA) products represent the most prominent example of a biopharmaceutical engineered in order to alter biological half-life [19]. Unmodified tPA, although an effective thrombolytic agent, displays a half-life of some 3 min after i.v. administration. 

Alteplase Alteplase is a drag that activates human tissue plasminogen (t-PA). It is a glycoprotein of molecular mass 68,000 that is synthesized by vascular endothelial cells. t-PA cells were first isolated from cultured human melanoma cells [56-58], but currently a genetically recombined form of rt-PA is genetically engineered. 

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