Effect of an intravitreal antisense oligonucleotide on vision in Leber congenital amaurosis due to a photoreceptor cilium defect.


:Photoreceptor ciliopathies constitute the most common molecular mechanism of the childhood blindness Leber congenital amaurosis. Ten patients with Leber congenital amaurosis carrying the c.2991+1655A>G allele in the ciliopathy gene centrosomal protein 290 (CEP290) were treated (ClinicalTrials.gov no. NCT03140969 ) with intravitreal injections of an antisense oligonucleotide to restore correct splicing. There were no serious adverse events, and vision improved at 3 months. The visual acuity of one exceptional responder improved from light perception to 20/400.


Nat Med


Nature medicine


Cideciyan AV,Jacobson SG,Drack AV,Ho AC,Charng J,Garafalo AV,Roman AJ,Sumaroka A,Han IC,Hochstedler MD,Pfeifer WL,Sohn EH,Taiel M,Schwartz MR,Biasutto P,Wit W,Cheetham ME,Adamson P,Rodman DM,Platenburg G,Tome MD,




Has Abstract


2019-02-01 00:00:00














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    authors: Kureishi Y,Luo Z,Shiojima I,Bialik A,Fulton D,Lefer DJ,Sessa WC,Walsh K

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    authors: Qi X,Yun C,Sun L,Xia J,Wu Q,Wang Y,Wang L,Zhang Y,Liang X,Wang L,Gonzalez FJ,Patterson AD,Liu H,Mu L,Zhou Z,Zhao Y,Li R,Liu P,Zhong C,Pang Y,Jiang C,Qiao J

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    authors: Igarashi T,Brown C,Azadegan A,Haigwood N,Dimitrov D,Martin MA,Shibata R

    更新日期:1999-02-01 00:00:00

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    authors: Spanagel R,Pendyala G,Abarca C,Zghoul T,Sanchis-Segura C,Magnone MC,Lascorz J,Depner M,Holzberg D,Soyka M,Schreiber S,Matsuda F,Lathrop M,Schumann G,Albrecht U

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    authors: Hanks BA,Jiang J,Singh RA,Song W,Barry M,Huls MH,Slawin KM,Spencer DM

    更新日期:2005-02-01 00:00:00

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    更新日期:1997-07-01 00:00:00

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    authors: He X,Lau EHY,Wu P,Deng X,Wang J,Hao X,Lau YC,Wong JY,Guan Y,Tan X,Mo X,Chen Y,Liao B,Chen W,Hu F,Zhang Q,Zhong M,Wu Y,Zhao L,Zhang F,Cowling BJ,Li F,Leung GM

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    authors: Bhang HE,Gabrielson KL,Laterra J,Fisher PB,Pomper MG

    更新日期:2011-01-01 00:00:00