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Why Choose Morpholinos

There is no other gene knockdown reagent (including siRNA, PNA, mPNA, S-DNA, and LNA) that combines the properties of stability, nuclease-resistance, efficacy, long-term activity, water-solubility, low toxicity and exquisite specificity. Only Morpholino oligos provide all of these.

Morpholinos provide much better specificity than RNAi, siRNA and phosphorothioate based oligos, greatly decreasing the chance of catastrophic off-target antisense effects. The catalytic proteins used by Argonaute-dependant RNAi or RNase-H dependant antisense allow modulation of gene expression for RNA with as little as 7 bases of complementarity, while a Morpholino needs about 15 bases of complementarity with its target to start knocking down gene expression. The 25-base Morpholinos typically synthesized are so effective that translation-blocking Morpholinos often decrease gene expression to levels undetectable by Western blot. The exquisite specificity of Morpholinos contributes to their extremely low toxicity and suitability for use in embryos, while off-target gene modulation makes siRNA unusable in most embryonic systems.

Anionic antisense can trigger non-antisense effects by interacting with cationic moieties of proteins. The non-ionic backbone of a Morpholino minimizes interactions with proteins, eliminating this mechanism for inducing non-antisense effects. Morpholinos do not trigger cellular responses by binding to Toll-like receptors, eliminating a confounding artifact associated with knockdowns using siRNA.

PNAs offer specificity similar to Morpholinos, but their low water solubility makes PNA experiments difficult. Morpholino oligos are usually soluble at several millimolar aqueous concentration.

An siRNA project often starts by screening sequences to find a reasonably effective one. This was also a required step with phosphorothioate antisense oligos. Because of their well-understood mechanism of action and their ability to invade secondary structure, it is common to see effective knockdown from the first Morpholino oligo designed.

Morpholino gene knockdowns have persisted as long as seven days after delivery into embryos, with similar long-term efficacy in cultured cells. Resistant to nucleases, dilution by growth and division of the cells reduces their activity and their activity can be attenuated by high transcription rates of their target RNA (e.g. actin).

As steric blocking oligos, Morpholinos can be used not only to block translation but also to alter mRNA splicing, to bind miRNAs or to block binding of miRNA or regulatory proteins to RNA targets. Splice-blocking Morpholinos allow researchers to delete targeted exons and even analyze specific splice-forms of a gene with multiple splice variants. Morpholinos can target a pri-miRNA or a pre-miRNA to inhibit miRNA maturation or target a miRNA or one of its targets to inhibit miRNA activity. Binding of a splice-regulatory protein can be prevented by protecting its binding site with a Morpholino oligo.

Gene Tools is the original manufacturer of Morpholino oligos for the research market. Many researchers are aware of the astounding success of Morpholinos in the developmental biology community. Because cytosolic delivery in embryos is solved by microinjection, Morpholinos have became the premier knockdown tool for developmental biology. The experimental challenges associated with delivery into the cytosol/nuclear compartment of cells have slowed the growing use of Morpholinos in the broader gene knockdown market, though electroporation or Endo-Porter allow convenient delivery into most cultured cell types and Vivo-Morpholinos enable delivery in intact adult animals, organ explants and cell cultures. Gene Tools is continually improving delivery of Morpholinos so that ALL researchers can make use of them for applications ranging from studying individual gene function in cultured cells to performing entire genome screens in vivo.

Why are Morpholinos already the preferred knockdown choice of vertebrate developmental biologists? It's not just the properties; it's also the company. Gene Tools provides extensive customer support to design your oligos and help you with your Morpholino experiments. Our coupling efficiencies are the highest in the industry and allow for purification producing the highest quality oligo available. Each Morpholino oligo ships with a MALDI-TOF QC spectrum documenting its purity. Unlike the "oligo houses," Gene Tools is committed ONLY to Morpholino oligos and Morpholino oligo delivery systems.

Here is a link to a paper comparing the mechanism of action of Morpholinos, siRNA and phosphorothioate oligos:
Summerton J. Morpholino, siRNA, and S-DNA Compared: Impact of Structure and Mechanism of Action on Off-Target Effects and Sequence Specificity. Med Chem. 2007;7(7):651-660

Here is a link to a document about designing translation blocking and splice blocking Morpholinos

We provide a web page of papers and protocols available for downloading.

You can also browse our database of Morpholino publications to learn more about the properties and effectiveness of Morpholino oligos.