Effect of erythroid enhancer on β globin gene expression

摘要

β-Thalassamia, one of the severe genetic diseases, is now being treated with gene therapy by transferring the normal human β globin gene into the patient's stem cells and making it stably and adequately express a long time, in recent years. Our previous work verified that a 36bp fragment containing the NFE-2/AP-1 protein binding site in 5' hypersensitive site 2 (5' HS2) raised the expression level of β globin gene in MEI cells by 2-fold after retroviral mediated gene transfer and had no significant negative effect on virus titer and provirus integration compared with β globin gene alone. However vectors containing 412bp or 732bp enhancer fragment all led to low virus titer and extremely unstable provirus. Therefore, an attempt has been made to look for the suitable length of erythroid enhancer fragment between 36bp and 412bp, in order that we can obtain the high level expression of transferred β globin gene in MEL cells with no significant influence on virus titer and provirus integration.