Could PYC's CPP be used for vaccines?, page-38

Are morpholinos [PMOs] inextricably linked to the future of precision medicine? There are two further questions: why? and if they do represent such an amazing building block for genetic medicine, what is the drawback?

The article Morpholino, siRNA, and S-DNA compared: impact of structure and mechanism of action on off-target effects and sequence specificity helps to explain the advantages of the morpholino platform. Note: S-DNA are phosphorothioate-linked DNA utilising a phosphorothioate backbone, the most widely used chemical modification in antisense oligonucleotides carrying a negative charge and allowing binding to various proteins. Morpholinos by comparison have a phosphorodiamidate backbone and a neutral charge.

Morpholinos are virtually free of off-target effects in part [or wholly] due to the fact they cannot electrostatically interact with proteins. Morpholinos also achieve exquisite sequence specificity in part [or wholly] due to the fact that they must bind to at least a total of 14 to 15 contiguous bases to form a gene transcript. My understanding is that the complex binding sequence allows it to uniquely target a selected gene.

If morpholinos are the future of precision medicine it will be because the neutral charge helps to ensure they are free of off-target effects while the exquisite binding sequence ensures that they can uniquely target a selected gene. Oh, there is one small problem they are hopeless at getting into cells which is in fact, the drawback.

In light of the false dawn of gene therapy, the biotech that can harness the unique properties of morpholinos could well play a dominant role in the treatment of genetically defined disease.