Morpholinos for adult animals

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Jon Moulton
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Morpholinos for adult animals

Vivo-Morpholinos enter the cells of adult organisms when administered by I.V. injection. Initial results in mouse, rat and adult zebrafish show activity of splice-blocking and translation-blocking Morpholinos in tissues after introduction of Vivo-Morpholinos into the blood. Delivery efficacy varies by tissue type, but this is far better activity than has been seen with bare Morpholino oligos.

Vivo-Morpholinos are Morpholino oligos covalently linked to octaguanidinium dendrimers. The dendrimers are synthesized on the Morpholino oligo while the oligos are still attached to their synthesis resin, then capped with guanidiniums. The oligos are then cleaved from the resin and the bases deprotected. This means that existing oligos cannot be modified to be Vivo-Morpholinos; addition of a delivery moiety must be specified prior to synthesis. Vivo-Morpholinos are available on the Gene Tools online store and are described on the Gene Tools website (http://www.gene-tools.com/vivomorpholinos), where you can find links to some gel images from splice-modification experiments in mouse.

The availability of Vivo-Morpholinos makes the specific and effective activities of Morpholino oligos available in many traditional animal model systems where Morpholinos were not effective in the past due to delivery issues. Highly specific Morpholino translation blocking, splice blocking and miRNA maturation inhibition are now feasible in adult rodents, allowing knockdowns without the known widespread off-target gene modulation associated with RNAi technologies and RNase-H dependent antisense.

Jon Moulton
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So far, there has been a

So far, there has been a presentation and now a paper reporting results with Vivo-Morpholinos in mice.

The paper reports delivery in transgenic mice with an EGFP splice-reporter system:
Li YF, Morcos PA. Design and Synthesis of Dendritic Molecular Transporter that Achieves Efficient in Vivo Delivery of Morpholino Antisense Oligo. Bioconjug Chem. 2008; 19:1461-70. Epub 2008 Jun 20

The presentation described the use of Vivo-Morpholinos in mdx mice, a mouse model of Duchenne muscular dystrophy:
Wu B, Li Y, Morcos PA, Doran TJ, Lu P, Lu QL. Restoration of Dystrophin Expression in Skeletal and Cardiac Muscle by Systemic Delivery of MorpholinoE23-Vivo Porter Oligonucleotide. 2008. Abstract 433, Annual Meeting of American Society of Gene Therapy, Boston, MA USA.