Identification of a novel muscle targeting peptide in mdx mice
Identification of a novel muscle targeting peptide in mdx mice
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DOI：
10.1016/j.peptides.2010.06.036
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发表时间：
2010-10-01
期刊：
影响因子：
3
通讯作者：
Wood, Matthew J. A.
中科院分区：
文献类型：
--
作者：
Seow, Yiqi;Yin, Haifang;Wood, Matthew J. A.
外显子跳跃寡核苷酸是一种针对杜氏肌营养不良症（DMD）的研究充分的治疗策略。尽管肌肉内和静脉内递送未修饰的寡核苷酸在动物模型中取得了显著的成功，但用简单的肽配体特异性靶向正常和营养不良肌肉的能力可以降低所需的治疗剂量并降低毒性的可能性。因此，利用12-mer肽文库对mdx小鼠进行了3轮体内噬菌体展示，并鉴定了具有靶向肌肉而非肝脏的潜力的肽基序。该基序显示出与乱序对照肽相比对C2 C12成肌细胞具有增强的结合亲和力，并且在C57 BL/6小鼠中尾静脉给药后，体内应用含有所鉴定基序的荧光素标记肽导致对心脏和四头肌的特异性增加。这项工作有许多潜在的应用寡核苷酸或药物输送到肌肉肌病。(C)2010年爱思唯尔公司All rights reserved.
Exon-skipping oligonucleotides are a well-researched therapeutic strategy for Duchenne's muscular dystrophy (DMD). Despite remarkable successes in animal models with intramuscular and intravenous delivery of unmodified oligonucleotides, the ability to specifically target both normal and dystrophic muscle with a simple peptide ligand could decrease the therapeutic dose required and reduce the potential for toxicity. Thus, 3 rounds of in vivo phage display utilizing a 12-mer peptide library were performed with mdx mice and a peptide motif with potential for targeting to muscle but not liver was identified. This motif was shown to have enhanced binding affinity to C2C12 myoblasts over a scrambled control peptide and in vivo application of a fluorescein-labeled peptide containing the identified motif resulted in increased specificity for the heart and quadriceps muscle after tail-vein administration in C57BL/6 mice. This work has many potential applications for oligonucleotide or drug delivery to muscle for myopathies. (C) 2010 Elsevier Inc. All rights reserved.