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Innate immune stimulation by Morpholinos in Xenopus?

The discussion of innate immune stimulation by Morpholinos in Xenopus continues.

Paraiso KD, Blitz IL, Zhou JJ, Cho KWY. Morpholinos Do Not Elicit an Innate Immune Response during Early Xenopus Embryogenesis. Dev Cell. 2019;49(4):643-50. doi:10.1016/j.devcel.2019.04.019
https://www.cell.com/developmental-cell/fulltext/S1534-5807(19)30316-8

Monday, May 20, 2019 - 14:37
Their mutants and their morphants show difering phenotypes: they suggest that more time is needed for compensation, mutants having enough but not morphants

These investigators suggest a reason their mutants and their morphants show different phenotypes. The mutant embryos have had time enough to compensate for the knockdowns, hiding aspects of the loss-of-funciton phenotype, while the acute knockdown of the Morpholino shows a phenotype during time insufficient for compensation.

Yang C-R, Rajkovic G, Daldello EM, Luong XG, Chen J, Conti M. The RNA binding protein DAZL functions as repressor and activator of maternal mRNA translation during oocyte maturation. bioRxiv. 2019;[preprint] doi:10.1101/598805

Wednesday, May 15, 2019 - 10:28
Antisense oligonucleotides to treat spinal muscular atrophy (Shift Pharmaceuticals)

Antisense oligonucleotides to treat spinal muscular atrophy
Shift Pharmaceuticals (University of Missouri)
Abstract for Midwest Drug Development Conference, Sept. 30-Oct. 1, 2019. Omaha NE.
https://www.mwdrugdevelopment.com/speakers/oligonucleotides-spinal-muscu...

Monday, May 6, 2019 - 10:13
Morpholinos: Research Tools and Therapeutics (Cell Press Selections)

New Cell Press Selections: Morpholinos: Research Tools and Therapeutics

Friday, April 26, 2019 - 14:07
Storage of Morpholinos: refrigerate or room temperature?

Morpholino oligos are completely chemically & biologically (enzymatically) stable sitting in water at 4C or at room temperature as long as the pH is not extreme. However, they undergo physical changes that can affect their biological activity. Chilled storage increases the tendency of the oligos to associate with container walls (this is especially a problem if the oligos undergo freeze-thaw cycles). Once a Morpholino has associated tightly with the wall of a container, it can be difficult or impossible to get the oligo back into solution at neutral pH.

Tuesday, April 23, 2019 - 08:01
Proposed mechanism underlying genetic compensation

Genetic paradox explained by nonsense. Wilkinson MF. Nature. 2019;568:179-180. doi: 10.1038/d41586-019-00823-5
https://www.nature.com/articles/d41586-019-00823-5

Genetic compensation triggered by mutant mRNA degradation. El-Brolosy MA et al. Nature. 2019;568:193-197. doi:10.1038/s41586-019-1064-z
https://www.nature.com/articles/s41586-019-1064-z

Thursday, April 11, 2019 - 13:46
Antibody validation by Morpholino

Here is an example of using Morpholinos for antibody validation.

Ratzan W, Rayaprolu V, Killian SE, Bradley R, Kohout SC. The voltage sensing phosphatase (VSP) localizes to the apical membrane of kidney tubule epithelial cells. PLoS ONE. 2019;14(4):e0209056. doi:10.1371/journal.pone.0209056

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209056

Wednesday, April 10, 2019 - 12:44
Paper: PTC-bearing mRNA elicits a genetic compensation response via Upf3a and COMPASS components

Another brick pulled from the wall concealing the mechanism of genetic compensation. Nonsense-mediated decay appears again.

Ma Z, Zhu P, Shi H, Guo L, Zhang Q, Chen Y, Chen S, Zhang Z, Peng J, Chen J. PTC-bearing mRNA elicits a genetic compensation response via Upf3a and COMPASS components. Nature. 2019;[Epub ahead of print] doi:10.1038/s41586-019-1057-y

https://www.nature.com/articles/s41586-019-1057-y

Wednesday, April 3, 2019 - 11:38
mutant-morphant disagreement in zebrafish - a story

Here is a story of mutant-morphant disagreement in zebrafish and its effects on one investigator's research. http://thenode.biologists.com/dead-ends-in-research-can-be-new-beginnings/research/

Tuesday, April 2, 2019 - 11:11
Antisense delivery enhancement strategies: meta-analysis

Comparison of enhancements to antisense delivery (peptides, dendrimers, etc.)

Assisted delivery of antisense therapeutics in animal models of heritable neurodegenerative and neuromuscular disorders: a systematic review and meta-analysis.

van der Bent ML, Paulino da Silva Filho O, van Luijk J, Brock R, Wansink DG.

Sci Rep. 2018 Mar 8;8(1):4181. doi: 10.1038/s41598-018-22316-7.

https://www.nature.com/articles/s41598-018-22316-7

Tuesday, March 26, 2019 - 08:54

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