Fructose Promotes Uptake and Activity of Oligonucleotides With Different Chemistries in a Context-dependent Manner in mdx Mice

Public Deposited

Downloadable Content

Download PDF


Attribute NameValues
  • Antisense oligonucleotide (AO)-mediated exon-skipping therapeutics shows great promise in correcting frame-disrupting mutations in the DMD gene for Duchenne muscular dystrophy. However, insufficient systemic delivery limits clinical adoption. Previously, we showed that a glucose/fructose mixture augmented AO delivery to muscle in mdx mice. Here, we evaluated if fructose alone could enhance the activities of AOs with different chemistries in mdx mice. The results demonstrated that fructose improved the potency of AOs tested with the greatest effect on phosphorodiamidate morpholino oligomer (PMO), resulted in a 4.25-fold increase in the number of dystrophin-positive fibres, compared to PMO in saline in mdx mice. Systemic injection of lissamine-labeled PMO with fructose at 25 mg/kg led to increased uptake and elevated dystrophin expression in peripheral muscles, compared to PMO in saline, suggesting that fructose potentiates PMO by enhancing uptake. Repeated intravenous administration of PMO in fructose at 50 mg/kg/week for 3 weeks and 50 mg/kg/month for 5 months restored up to 20% of wild-type dystrophin levels in skeletal muscles with improved functions without detectable toxicity, compared to untreated mdx controls. Collectively, we show that fructose can potentiate AOs of different chemistries in vivo although the effect diminished over repeated administration.
  • This is the publisher’s final pdf. The article is copyrighted by the author(s) and published by Nature Publishing Group on behalf of the American Society of Gene and Cell Therapy. It can be found at:
  • Keywords: antisense oligonucleotide, Duchenne muscular dystrophy, exon skipping, fructose
Resource Type
Date Available
Date Issued
  • Cao, L., Han, G., Lin, C., Gu, B., Gao, X., Moulton, H. M., ... & Yin, H. (2016). Fructose Promotes Uptake and Activity of Oligonucleotides With Different Chemistries in a Context-dependent Manner in mdx Mice. Molecular Therapy—Nucleic Acids, 5, e329. doi:10.1038/mtna.2016.46
Journal Title
Journal Volume
  • 5
Rights Statement
Funding Statement (additional comments about funding)
  • This work was supported by National Key Basic Research Program of China (973) (No. 2012CBA01305, 2012CB932503); National Natural Science Foundation of China (No. 81361128013, 81273420 and 81301526) and Key Program of National Natural Science Foundation of Tianjin (No. 14JCZDJC36000).



This work has no parents.