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Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds (review)

Review article
Nan Y, Shang Y-J. Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds. Front Microbiol. 2018;9:750. doi:10.3389/fmicb.2018.00750
https://www.frontiersin.org/articles/10.3389/fmicb.2018.00750/full

Monday, April 23, 2018 - 07:33
BLAST homology: screening predicted specificity

It is always prudent to screen proposed oligo sequence for potential off-target RNA interactions using BLAST. Partial homologies between a Morpholino's inverse complement and an RNA which are reported by BLAST are often in regions of the RNA where binding a Morpholino is unlikely to alter gene expression. If there is significant homology in a region where binding a Morpholino is likely to alter a transcript's expression, have us design another oligo.

Thursday, April 5, 2018 - 09:31
Fish mutant, where is thy phenotype?

"Due to genetic compensation, phenotypically wild-type mutants can become refractive to morpholino-induced phenotypes, providing a critical test both for genetic compensation and for the specificity of morpholino phenotypes."

Balciunas D. Fish mutant, where is thy phenotype? PLoS Genet. 2018;14(2):e1007197.
https://doi.org/10.1371/journal.pgen.1007197

Thursday, February 22, 2018 - 11:40
Cardiac Ventricular Injection in Zebrafish Larva

This is an interesting technique for later-stage zebrafish embryo treatment, involving pulsed injection of a mixture of Morpholino and Endo-Porter into the heart. I think this might push the limit of solubility for many Morpholino sequences. They are reporting good systemic delivery -- see the video for fluorescent images of the oligo distribution.

Wednesday, February 14, 2018 - 15:27
Patent on central nervous system delivery of Morpholinos by low osmolar contrast agents

This one looks interesting. Morpholino and 2'-MOE activities are compared in SMA models.

United States Patent Application 20180030443
February 1, 2018
Inventors: Burghes; Arthur; (Columbus, OH) ; Porensky; Paul; (Worthington, OH) ; Kaspar; Brian; (New Albany, OH)

NON-IONIC, LOW OSMOLAR CONTRAST AGENTS FOR DELIVERY OF ANTISENSE OLIGONUCLEOTIDES AND TREATMENT OF DISEASE

Wednesday, February 7, 2018 - 11:43
Skipping Multiple Exons: Review of DMD Morpholino, Vivo-Morpholino & PPMO work

Review of DMD multiple exon skipping with Morpholino, Vivo-Morpholino & PPMO by Toshifumi Yokota's group.

Skipping Multiple Exons to Treat DMD-Promises and Challenges.

Aslesh T, Maruyama R, Yokota T.

Biomedicines. 2018 Jan 2;6(1). pii: E1. doi: 10.3390/biomedicines6010001. Review.

http://www.mdpi.com/2227-9059/6/1/1

Monday, January 8, 2018 - 07:46
Morpholino-based skipping of an exon caused inclusion of another exon, following that transcipt's pattern of normal alternative splicing.

Here is an example of an unusual outcome from modifying splicing. Vivo-Morpholinos targeting exon 9 caused skipping of exon 9 and inclusion of exon 10. In normal alternative splicing of this RNA, either exon 9 is included and exon 10 is excised (Pkm1) or exon 9 is excised and exon 10 is excluded (Pkm2).

Wednesday, December 20, 2017 - 12:00
Gel retardation assay using RNA with a complementary Morpholino

This image is of a gel retardation assay using RNA with a complementary Morpholino altering its migration.

https://static-content.springer.com/esm/art%3A10.1007%2Fs00705-017-3666-...

Tuesday, December 19, 2017 - 14:15
Paper: Hybrid splicing minigene and antisense oligonucleotides as efficient tools to determine functional protein/RNA interactions

This paper describes setting up systems to determine splicing-related protein-RNA interactions; this might be especially useful for confirming whether a particular putatuve splice-regulatory protein binding site is actually involved in modulating splicing. The oligos reported were not Morpholinos, but I expect this system would be compatible with Morpohlinos.

Hybrid splicing minigene and antisense oligonucleotides as efficient tools to determine functional protein/RNA interactions.

Cywoniuk P, Taylor K, Sznajder ŁJ, Sobczak K.

Monday, December 18, 2017 - 09:18
Chemistry, mechanism and clinical status of antisense oligonucleotides and duplex RNAs

This is an overview of various antisense drugs, approved, withdrawn, and in clinical trials, along with an introduction to various intisense structural types and modes of action.

Shen X, Corey DR. Chemistry, mechanism and clinical status of antisense oligonucleotides and duplex RNAs. Nucleic Acid Research. 2017;[Epub ahead of print] doi:/10.1093/nar/gkx1239
https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkx1239/473...

Tuesday, December 12, 2017 - 08:42

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