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Splicing mutations in human genetic disorders: Review

This is an open-access review covering the mechanism of eukaryotic RNA splicing and diseases caused by mutations in regions affecting splicing.

Abramowicz A, Gos M. Splicing mutations in human genetic disorders: examples, detection, and confirmation. J Appl Genet. 2018. doi: 10.1007/s13353-018-0444-7
https://rd.springer.com/article/10.1007%2Fs13353-018-0444-7

Tuesday, April 24, 2018 - 08:55
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 transcript'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

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