Application of Antisense Conjugates for the Treatment of Myotonic Dystrophy Type 1.
Application of Antisense Conjugates for the Treatment of Myotonic Dystrophy Type 1.
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DOI：
10.3390/ijms24032697
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发表时间：
2023-01-31
影响因子：
5.6
通讯作者：
Varela, Miguel A.
中科院分区：
文献类型：
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作者：
Stoodley, Jessica;Vallejo-Bedia, Francisco;Seone-Miraz, David;Debasa-Mouce, Manuel;Wood, Matthew J. A.;Varela, Miguel A.
关键词：
强直性肌营养不良1型（DM1）是最常见的肌营养不良症之一，并且可以潜在地用反义疗法减少突变体DMPK、靶向miRNA或其结合位点或通过阻断MBNL1从重复序列置换的机制来治疗。未缀合的反义分子能够在小鼠模型中纠正疾病表型，但它们在DM 1患者中全身递送时显示出差的肌肉渗透。为了克服这一挑战，研究集中在使用与脂质、细胞穿透肽或抗体的生物缀合来改善反义疗法的治疗窗和生物分布。反义缀合物能够在分子和功能水平上诱导DM1病理学的持久校正，并且还有效地穿透难以到达的组织如心肌。以临床相关水平递送至CNS仍然具有挑战性，并且可能需要使用替代给药途径来改善DM 1患者经历的一些症状。随着目前临床试验中的几种反义疗法，为患者实现临床批准的治疗的前景从未如此有希望。
Myotonic dystrophy type 1 (DM1) is one of the most common muscular dystrophies and can be potentially treated with antisense therapy decreasing mutant DMPK, targeting miRNAs or their binding sites or via a blocking mechanism for MBNL1 displacement from the repeats. Unconjugated antisense molecules are able to correct the disease phenotype in mouse models, but they show poor muscle penetration upon systemic delivery in DM1 patients. In order to overcome this challenge, research has focused on the improvement of the therapeutic window and biodistribution of antisense therapy using bioconjugation to lipids, cell penetrating peptides or antibodies. Antisense conjugates are able to induce the long-lasting correction of DM1 pathology at both molecular and functional levels and also efficiently penetrate hard-to-reach tissues such as cardiac muscle. Delivery to the CNS at clinically relevant levels remains challenging and the use of alternative administration routes may be necessary to ameliorate some of the symptoms experienced by DM1 patients. With several antisense therapies currently in clinical trials, the outlook for achieving a clinically approved treatment for patients has never looked more promising.
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影响因子：
16.6
作者：
Freyermuth F;Rau F;Kokunai Y;Linke T;Sellier C;Nakamori M;Kino Y;Arandel L;Jollet A;Thibault C;Philipps M;Vicaire S;Jost B;Udd B;Day JW;Duboc D;Wahbi K;Matsumura T;Fujimura H;Mochizuki H;Deryckere F;Kimura T;Nukina N;Ishiura S;Lacroix V;Campan-Fournier A;Navratil V;Chautard E;Auboeuf D;Horie M;Imoto K;Lee KY;Swanson MS;de Munain AL;Inada S;Itoh H;Nakazawa K;Ashihara T;Wang E;Zimmer T;Furling D;Takahashi MP;Charlet-Berguerand N
通讯作者：
Charlet-Berguerand N
影响因子：
4
作者：
Crooke ST
通讯作者：
Crooke ST
Antagomir-218的临床前表征是肌营养不良症的潜在治疗方法。
DOI：
10.1016/j.omtn.2021.07.017
发表时间：
2021-12-03
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Cerro-Herreros E;González-Martínez I;Moreno N;Espinosa-Espinosa J;Fernández-Costa JM;Colom-Rodrigo A;Overby SJ;Seoane-Miraz D;Poyatos-García J;Vilchez JJ;López de Munain A;Varela MA;Wood MJ;Pérez-Alonso M;Llamusí B;Artero R
通讯作者：
Artero R
影响因子：
4.5
作者：
Huguet, Aline;Medja, Fadia;Gourdon, Genevieve
通讯作者：
Gourdon, Genevieve
影响因子：
5.1
作者：
通讯作者：
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