TitleAggregation and Disaggregation of Morpholino Oligomers in Solution.
Publication TypeJournal Article
Year of Publication2017
AuthorsChow, G, Morcos, PA, Moulton, HM
JournalMethods Mol Biol
Date Published2017
KeywordsBase Pairing, Base Sequence, Chromatography, High Pressure Liquid, Morpholinos, Oligonucleotides, Antisense, Solubility, Solutions

Morpholino oligomers are effective antisense molecules to regulate gene expression and the US FDA has approved a Morpholino drug for the treatment of Duchenne muscular dystrophy. However, it has been observed that the antisense activities of aqueous solutions of some Morpholinos decrease over time. We hypothesize that the decreased activity is caused by the formation of soluble aggregates of the Morpholinos. Here, we analyzed three Morpholino sequences by size exclusion chromatography and found two of them have over time formed soluble aggregates in water. The degree of aggregation is sequence-, temperature-, and time-dependent. We describe a simple procedure for detecting and breaking down the aggregates to return the Morpholinos to their monomeric forms.

Alternate JournalMethods Mol Biol
PubMed ID28364231