Can colorectal delivery technology provide a platform for enteral oligonucleotide-based therapeutics?

Murakami, Masahirô; Watanabe, Chie

doi:10.5582/ddt.2016.01070

Cited by 2 publications

(2 citation statements)

References 17 publications

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“…On the other hand, this strategy not only applies to the rectal absorption of polypeptides but also can be expanded to other biomedicines such as oligonucleotides, which are poorly permeable across the mucosa and unstable against enzymes in the intestine. We demonstrated that our rectal siRNA delivery technique using lipid nanoparticles provided therapeutic gene silencing in the liver through its delivery via the lymphatic route (37,38). Feasibility of our dimple-type suppository to rectal oligonucleotide delivery is now under investigation.…”

Section: Discussionmentioning

confidence: 92%

Improved systemic delivery of insulin by condensed drug loading in a dimpled suppository

Matsumoto

Murakami

Watanabe

et al. 2017

DD&T

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Section: Discussionmentioning

confidence: 92%

Improved systemic delivery of insulin by condensed drug loading in a dimpled suppository

Matsumoto

Murakami

Watanabe

et al. 2017

DD&T

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“…Eteplirsen and Nusinersen), and exon-skipping therapy has become a reality. While AONs offer a specific way to modulate splicing in a therapeutic manner, some hurdles must be overcome for the orally available antisense drugs3233. Compared to AONs, small chemical compounds may not be as specific, but more advantageous for the synthesis cost and the oral availability.…”

Section: Discussionmentioning

confidence: 99%

Development of an orally available inhibitor of CLK1 for skipping a mutated dystrophin exon in Duchenne muscular dystrophy

Sako

Ninomiya

Okuno

et al. 2017

Sci Rep

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Duchenne muscular dystrophy (DMD) is a fatal progressive muscle-wasting disease. Various attempts are underway to convert severe DMD to a milder phenotype by modulating the splicing of the dystrophin gene and restoring its expression. In our previous study, we reported TG003, an inhibitor of CDC2-like kinase 1 (CLK1), as a splice-modifying compound for exon-skipping therapy; however, its metabolically unstable feature hinders clinical application. Here, we show an orally available inhibitor of CLK1, named TG693, which promoted the skipping of the endogenous mutated exon 31 in DMD patient-derived cells and increased the production of the functional exon 31-skipped dystrophin protein. Oral administration of TG693 to mice inhibited the phosphorylation of serine/arginine-rich proteins, which are the substrates of CLK1, and modulated pre-mRNA splicing in the skeletal muscle. Thus, TG693 is a splicing modulator for the mutated exon 31 of the dystrophin gene in vivo, possibly possessing therapeutic potential for DMD patients.

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Can colorectal delivery technology provide a platform for enteral oligonucleotide-based therapeutics?

Cited by 2 publications

References 17 publications

Improved systemic delivery of insulin by condensed drug loading in a dimpled suppository

Improved systemic delivery of insulin by condensed drug loading in a dimpled suppository

Development of an orally available inhibitor of CLK1 for skipping a mutated dystrophin exon in Duchenne muscular dystrophy

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