RNA repair restores hemoglobin expression in IVS2-654 thalassemic mice

被引：64

作者：

Svasti, Saovaros ^{[2
,3
]}

Suwanmanee, Thipparat ^{[2
]}

Fucharoen, Suthat ^{[3
]}

Moulton, Hong M. ^{[4
]}

Nelson, Michelle H. ^{[4
]}

Maeda, Nobuyo ^{[1
]}

Smithies, Oliver ^{[1
]}

Kole, Ryszard ^{[2
,4
]}

机构：

[1] Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, Dept Pharmacol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[3] Mahidol Univ, Thalassemia Res Ctr, Inst Sci & Technol Res & Dev, Nakhon Pathom 73170, Thailand

[4] AVI BioPharma, Corvallis, OR 97333 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 04期

基金：

美国国家卫生研究院;

关键词：

oligonucleotides; RNA splicing; thalassemia; therapy; morpholino oligomers; ANTISENSE OLIGONUCLEOTIDES; ERYTHROID-CELLS; GENE-EXPRESSION; BETA-THALASSEMIA; MESSENGER-RNA; RESTORATION; DELIVERY; MUTATION;

D O I：

10.1073/pnas.0812436106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Repair of beta-globin pre-mRNA rendered defective by a thalassemia-causing splicing mutation, IVS2-654, in intron 2 of the human beta-globin gene was accomplished in vivo in a mouse model of IVS2-654 thalassemia. This was effected by a systemically delivered splice-switching oligonucleotide (SSO), a morpholino oligomer conjugated to an arginine-rich peptide. The SSO blocked the aberrant splice site in the targeted pre-mRNA and forced the splicing machinery to reselect existing correct splice sites. Repaired beta-globin mRNA restored significant amounts of hemoglobin in the peripheral blood of the IVS2-654 mouse, improving the number and quality of erythroid cells.

引用

页码：1205 / 1210

页数：6

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