Exon-skipping therapy: a roadblock, detour, or bump in the road?
Exon-skipping therapy: a roadblock, detour, or bump in the road?
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DOI：
10.1126/scitranslmed.3008873
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发表时间：
2014-04-02
影响因子：
17.1
通讯作者：
McNally EM
中科院分区：
文献类型：
--
作者：
Hoffman EP;McNally EM
杜氏肌营养不良症（DMD）每5000个新生儿中就有1个患病。这些男孩在婴儿和幼儿时期看起来很健康，但随后经历了令人心碎的衰退，因为肌肉组织逐渐萎缩，使患者在十几岁后期无法行动。心脏和呼吸肌也同样衰弱，影响寿命。DMD在20世纪50年代充当了群体遗传学的试验台，在80年代充当了基因鉴定方法（反向遗传学）的试验台，并将分子诊断整合到患者诊断和家庭咨询中。抗肌营养不良蛋白基因是人类基因组中最大的基因，拥有230万个碱基对，并且在所有人类基因中具有最高的已知自发突变率。尽管我们在了解DMD的分子基础方面取得了长足的进展，但将这些进展转化为改善患者护理的过程却非常缓慢。干细胞移植和替代基因治疗的早期成功迹象遇到了技术障碍和免疫障碍，这些障碍一直无法逾越。
Duchenne muscular dystrophy (DMD) affects 1in 5,000 newborn males. These boys appear healthy as infants and young children, but then experience a heartbreaking decline, as muscle tissue gradually wastes away, leaving patients nonambulant by their late teens. The heart and respiratory muscles are similarly weakened, compromising life span. DMD has served as a test bed for population genetics in the 1950’s, gene identification methods (reverse genetics) in the 1980’s, and the integration of molecular diagnostics into patient diagnosis and family counseling. Additional landmarks are held by the dystrophin gene: It is the largest in the human genome—2.3 million base pairs—and has the highest known spontaneous mutation rate of all human genes. Although we have made robust progress in understanding the molecular basis of DMD, translation of these advances to improvements in patient care has been painfully slow. Early hints of success with stem cell transplantation and replacement gene therapy hit technical roadblocks of delivery and immunological barriers that have remained persistently impassable.
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影响因子：
158.5
作者：
Goemans, Nathalie M.;Tulinius, Mar;van Deutekom, Judith C.
通讯作者：
van Deutekom, Judith C.
影响因子：
168.9
作者：
Cirak, Sebahattin;Arechavala-Gomeza, Virginia;Guglieri, Michela;Feng, Lucy;Torelli, Silvia;Anthony, Karen;Abbs, Stephen;Garralda, Maria Elena;Bourke, John;Wells, Dominic J.;Dickson, George;Wood, Matthew J. A.;Wilton, Steve D.;Straub, Volker;Kole, Ryszard;Shrewsbury, Stephen B.;Sewry, Caroline;Morgan, Jennifer E.;Bushby, Kate;Muntoni, Francesco
通讯作者：
Muntoni, Francesco
影响因子：
82.9
作者：
Alter, J;Lou, F;Lu, QL
通讯作者：
Lu, QL
影响因子：
4.2
作者：
Malerba, Alberto;Thorogood, Francesca C.;Graham, Ian R.
通讯作者：
Graham, Ian R.
影响因子：
15.9
作者：
MATSUO, M;MASUMURA, T;NAKAMURA, H
通讯作者：
NAKAMURA, H