TRANSCRIPTIONAL ACTIVITY OF THE CD45 GENE PROMOTER IN RETROVIRAL VECTOR CONSTRUCTS

Both specific and housekeeping transcriptional control elements have b een successfully used to generate retroviral vectors that express in a stable tissue specific manner. However, no such vectors have been dev eloped specifically for expression in haematopoietic cells. This paper describes the construction of retroviral vectors incorporating sequen ces from the promoter region of the murine CD45 (leucocyte common anti gen) gene and using the human alpha-L-iduronidase cDNA as a reporter g ene. These vectors were tested for expression of the alpha-L-iduronida se gene in skin fibroblasts and a lymphoblastiod cell line which is pe rmissive for CD45 expression, derived from patients with mucopolysacch aridosis type I(MPS I, alpha-L-iduronidase deficiency). The results ob tained demonstrate that, in the context of a retroviral construct, the activity of the CD45 gene promoter in lymphocytes and fibroblasts par allels the activity of the retroviral long terminal repeat (LTR). Thes e results suggest that additional transcriptional control elements fro m the CD45 gene, or other haematopoietic specific genes, will be neces sary for the construction of a haematopoietic specific vector.