Blood proteins from transgenic animal bioreactors

摘要: T HE TRANSMISSION of viruses by blood transfusion and replacement therapy with human plasma proteins has caused serious concern in recent years, eliciting several changes the preparation products. The selection donors, rigorous screening collected blood, virucidal procedures introduced purification have nearly eliminated problems immunodeficiency virus hepatitis B transmission, plasma-derived are generally considered to be safe. ~ Past experiences fractionators product safety made them cautious, as shown voluntary withdrawal intravenous immunoglobulin (IGIV) products 1994 after reports C transmission Europe, albumin factor VIII (FVIII) concentrates containing a unit from Creutzfeldt-Jakob disease (CJD)-affected donor, intramuscular ilnmunoglobulin early 1995. discussion on contamination infectious agents that could transmit neurodegenerative diseases like CJD or Gerstmann-Str~iussler-Scheinker disease, transfusion-associated bacterial sepsis parasitic Chagas is ongoing. production recombinant an alternative, which will increase available amount product. More important, lower cost permit its use prophylaxis for oral administration. As result, new treatment regimens, such topical application a~ antitrypsin (a1AT) psoriasis may become feasible. Indeed, increasing acceptance FVIII (rFVIII) both clinicians patients provided added impetus search sources proteins. widespread transgenic animals basic research, 2 development models, 3 genetic improvement livestock 4 led considerable interest employing genetically engineered therapeutic proteins, 5,6 alternative complement eukaryotic cell culture systems. Human being expression those commonly used therapy, IX (FIX), 7,8 FVIII, 9 protein (PC), 1~ antithrombin III (ATIII) (H. Meade, personal communication, February 1995), well serum (HSA) ~2, ~I-AT, 13-14 hemoglobin (Hb),~s fibrinogen (Velander et al: Unpublished observations, 1994). In approach, synthesis targeted selected type organ, enabling harvested body fluids milk, saliva, urine. Since 1987, numerous potential been successfully noninvasive methods mice farm rabbits, sheep, pigs, goats, 16A7 leading commercial well-established technologies. Questions respect transgene inheritance stability, appropriate posttranslational modifications heterologous industrial procedures, regulatory affairs now emerged, there limited data published long-term effects foreign animal "bioreactor" (TAB). this review, authors discuss benefits limitations express their views possible impact medicine.