Recombinant proteins for genetic disease

The era of molecular biology has led to the development of powerful tools capable of generating therapeutics for genetic disorders. Although there is much current emphasis placed on the development of ‘gene therapy’ for human disease, developments in the production and availability of recombinant proteins are likely to have a more substantial impact on genetic disease in the short term. The clinical evaluation of recombinant or purified proteins serves as an initial ‘proof of principle’ of gene‐based therapies and thus should expedite advances in this area. Current examples include the use of bovine adenosine deaminase for a form of severe combined immune deficiency (SCID) (Hilman BC, Sorensen RU. Management options: SCIDS with adenosine deaminase deficiency. Ann Allergy 72: 1994: 395–403) and glucocerebrosidase for Gaucher disease (Niederau C, vom Dahl S, Haussinger D. First long‐term results of imiglucerase therapy of type 1 Gaucher disease. Eur J Med Res 1998: 3: 25–30). The success of these two enzyme replacement regimes in human clinical trials has been a main impetus for the development of gene‐based therapies for these disorders. The ‘molecularization of medicine’ has led to a more thorough understanding of the molecular basis of disease and disease pathogenesis. The availability of recombinant proteins and the development of appropriate delivery systems will result in more widespread use of these agents. Protein engineering will generate agents with novel functions as is already witnessed with the generation of fusion proteins. This review will highlight advances in the use of recombinant proteins for genetic disease and future potential uses of recombinant proteins.