Prospects for correction of thalassemia by genetic engineering.

The thalassemias are diverse genetic disorders characterized by abnormal synthesis rates of one or more proteins constituting hemoglobin (globin-chains). In the beta-thalassemias, genes encoding the beta-globin chain are intact but are abnormally transcribed or, less often, translated. In the alpha-thalassemias, genes encoding the alpha-globin chain are often deleted; abnormal transcription can also occur. The human beta- and alpha-globin genes were molecularly cloned. This review considers attempts to introduce these genes in mammalian cells by physical techniques such as chromosome transfer, transfection, fusion, micro-injection, electroporation and homologous recombination or by using DNA or RNA viruses, such as retroviruses. Currently, inefficient gene expression in host cells and the need for precise cognate regulation of globin gene expression are the major limitations to applying genetic engineering to thalassemia.