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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
Impurities in Oligonucleotide Drug Substances and Drug Products

Here's an interesting article on oligo drug impurities, written from a phosphorothioate perspective but with many ideas potentially applicable to Morpholino GMP production.

Tuesday, December 12, 2017 - 08:36
Why use 0.1N HCl to measure Morpholino concentration by UV spec?

Here is an excerpt from a letter Jim Summerton recently wrote in which he described the reason why Morpholinos are quantitated by measuring UV absorbance at 265 nm in 0.1N HCl.

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Tuesday, November 28, 2017 - 09:45
Targeting internal exon caused intron inclusion: example of a less-common outcome

Here is an example where targeting an internal exon of a pre-mRNA caused inclusion of the adjacent intron, an unusual outcome.

Vierstraete J, Willaert A, Vermassen P, Coucke PJ, Vral A, Claes KBM. Accurate quantification of homologous recombination in zebrafish: brca2 deficiency as a paradigm. Sci Rep. 2017;7:16518. doi:10.1038/s41598-017-16725-3

https://www.nature.com/articles/s41598-017-16725-3

Tuesday, November 28, 2017 - 08:27

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