The main objective of the proposed research is to correct abnormal splicing of ?-globin pre-mRNA with antisense oligonucleotide ex vivo (Specific Aim 1) and in in vivo (Specific Aim 2) in the IVS2-654 and HbE mouse models. The Specific Aims will be:
1. To establish antisense oligonucleotide treatment of mononuclear erythroid cells from the bone marrow of IVSII-654 mouse, HbE mouse or IVSII-654/HbE mouse results in correct expression of human -globin mRNA and protein.
2. To treat the mice with the best antisense oligonucleotides identified in 1.
