@article {117545,
	title = {Correction of aberrant pre-mRNA splicing by antisense oligonucleotides in beta-thalassemia Egyptian patients with IVSI-110 mutation.},
	journal = {Journal of pediatric hematology/oncology},
	volume = {30},
	year = {2008},
	month = {2008 Apr},
	pages = {281-4},
	abstract = {<p>The splicing mutation in intron 1 of beta-globin gene (IVS1-110) is the most common mutation in Egyptian thalassemics that causes aberrant splicing of pre-mRNA and deficient beta-globin chain synthesis. Antisense oligonucleotides (ASONs) are compounds that redirect pre-mRNA splicing and modify gene expression. Our aim was ex vivo correction of the aberrant splicing of beta-globin110 pre-mRNA by ASON against the 3{\textquoteright} aberrant splice site. Peripheral blood mononuclear cells of 10 thalassemic patients with IVS1-110 mutation were duplicated and 1 was treated with 20 micromoL/mL morpholino ASON targeted against the 3{\textquoteright} aberrant splice site. The level of total hemoglobin (Hb), fetal Hb, and mRNA were estimated in the duplicate samples. Five cases (50\%) showed correction with ASON treatment, of which 2 cases showed the appearance of corrected mRNA band with absence of the aberrant band and 3 cases showed an increased ratio of the corrected to the aberrant mRNA band from 2:1 to 3:1, and 4:1. The total Hb showed significant increase in the 5 corrected cases. In conclusion, ASON can restore correct splicing of beta-globin pre-mRNA leading to correct gene product in cultured erythropoietic cells. These results suggest the applicability of ASON for the treatment of thalassemia.</p>
},
	keywords = {Adolescent, Adult, Alternative Splicing, beta-Thalassemia, Child, Child, Preschool, Egypt, Female, Globins, Homozygote, Humans, Introns, Male, Mutation, Oligonucleotides, Antisense, Reverse Transcriptase Polymerase Chain Reaction, RNA Precursors, RNA Splicing},
	issn = {1077-4114},
	doi = {10.1097/MPH.0b013e3181639afe},
	author = {Amal El-Beshlawy and Mostafa, Azza and Ilham Youssry and Hala Gabr and Mansour, Iman M and El-Tablawy, Manar and Mona Aziz and Hussein, Ibtissam R}
}
