2023年10月2日 · 其中，DG9 肽已被确定为一种多功能 CPP，由于其独特的结构特征，在增强基于 ASO 的治疗药物的递送方面具有显着的潜力。 值得注意的是，在磷酸二酰胺吗啉低聚物 (PMO) 的背景下，DG9 在增强递送的同时保持有利的毒性特征方面表现出了良好的前景。

We first evaluate the efficacy of systemic DG9-PMO treatment in this model using a single-exon (exon 51)–skipping approach. We then apply the DG9 modification to the minimized exons 45 to 55–skipping mixture developed in this study, and determine its potential as a multiexon-skipping therapy for DMD.

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Development of DG9 peptide-conjugated single- and multi-exon skipping therapies for the treatment of Duchenne muscular dystrophy Today’s pick from PNASNews is again from the Prof. Toshi Yokota group.

2022年3月1日 · Development of DG9 peptide-conjugated single- and multi-exon skipping therapies for the treatment of Duchenne muscular dystrophy March 2022 Proceedings of the National Academy of Sciences 119 (9)

2023年10月2日 · Antisense oligonucleotide-based (ASO) therapeutics have emerged as a promising strategy for the treatment of human disorders. Charge-neutral PMOs have promising biological and pharmacological properties for antisense applications. Despite their great potential, the efficient delivery of these therapeutic agents to target cells remains a major obstacle to their widespread use. Cellular uptake ...

We also demonstrated DG9-conjugated PMO localized in nuclei in the spinal cord and brain after subcutaneous injections. Our data identify DG9 peptide conjugation as a powerful way to improve the efficacy of AO-mediated splice modulation.

Here, we developed a more economical approach to skip DMD exons 45 to 55 (a strategy that could treat nearly half of all DMD patients) and identified DG9 peptide conjugation as a powerful way to improve exon skipping efficiencies in vivo.

2022年5月19日 · Development of DG9 peptide-conjugated single- and multi-exon skipping therapies for the treatment of Duchenne muscular dystrophy By Zachary Coulson and James J. Dowling Program for Genetics and Genome Biology, Hospital for Sick Children Department of Molecular Genetics, University of Toronto Publication (February 2022) Rowel, K., Lim, Q., Yokota, T. et al. Development of DG9 peptide-conjugated ...

We also found that conjugating DG9, a cell-penetrating peptide, to PMOs improved single-exon 51 skipping, dystrophin restoration, and muscle function in hDMDdel52; mdx mice. Local administration of a minimized exons 45 to 55–skipping …

2023年12月18日 · Among these, the DG9 peptide has been identified as a versatile CPP with remarkable potential for enhancing the delivery of ASO-based therapeutics due to its unique structural features. Notably, in the context of PMOs, DG9 has shown promise in enhancing delivery while maintaining a favorable toxicity profile.