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Invention and Early History of Morpholinos: From Pipe Dream to Practical Products.
Beginning with my concept in 1969 to treat disease at the nucleic acid level using antisense nucleic acids, antisense has evolved to the current Morpholino oligos. Morpholinos have been the dominant gene knockdown system in developmental biology. Lack of delivery technologies has limited their use in adult animals (including humans), though alteration in muscles in Duchenne muscular dystrophy (DMD) allows delivery into adult muscle. Morpholinos are currently in Phase 3 clinical trials for DMD and a Morpholino oligo for skipping dystrophin exon 51 has been approved by the US FDA. With improved delivery techniques, such as those in development at Gene Tools, therapeutic Morpholinos for many difficult-to-treat diseases will be possible. Initial applications are expected to be custom cocktails of delivery-enabled Morpholinos for treating cancers.
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