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Targeting alternative splicing to upregulate protein expression

Potential application in antisense therapeutics: upregulation of targeted protein expression

Here is a new paper demonstrating techniques for targeting steric-blocking antisense oligos to alternatively-spliced transcripts undergoing NMD to alter the splicing and recover transcripts encoding useful proteins. This is a technique for antisense upregulation of a protein activity.

Thursday, July 9, 2020 - 13:45
Clinical antisense review (2020)

Clinical antisense review
Dhuri K, Bechtold C, Quijano E, Pham H, Gupta A, Vikram A, Bahal R. Antisense Oligonucleotides: An Emerging Area in Drug Discovery and Development. J Clin Med. 2020;9(6):2004. doi:10.3390/jcm9062004

Friday, June 26, 2020 - 12:18
Retention of the last intron

Here are a few publications addressing Morpholinos and retention of the last intron.

See the section: Retention of wnt11b Intron 4 Recapitulates the Failure to Form Somites in tra2b Morphants
Dichmann DS, Walentek P, Harland RM. The Alternative Splicing Regulator Tra2b Is Required for Somitogenesis and Regulates Splicing of an Inhibitory Wnt11b Isoform. Cell Rep. 2015 Jan 21. pii: S2211-1247(14)01099-7. doi: 10.1016/j.celrep.2014.12.046. [Epub ahead of print].

Wednesday, May 6, 2020 - 09:43
Presentations/posters from the 2020 MDA conference involving Morpholinos

Long-term Safety & Efficacy of Golodirsen in Male Patients with Duchenne Muscular Dystrophy (DMD) Amenable to Exon 53 Skipping

PMO-based miRNA site blocking oligo (SBO) mediated utrophin upregulation in mdx mice, a therapeutic approach for Duchenne Muscular Dystrophy (DMD)

Thursday, March 26, 2020 - 16:00
Viltepso (Morpholino drug) approved for DMD in Japan

Nippon Shinyaku has received marketing approval in Japan for Viltepso, a Morpholino targeting human dystrophin exon 53 for treatment of some mutations causing Duchenne muscular dystrophy.

Wednesday, March 25, 2020 - 09:44
Report of compensation in mutants

Genetic Compensation of γ CaMKII, an Evolutionarily Conserved Gene.

Rothschild SC, Ingram SR, Lu FI, Thisse B, Thisse C, Parkerson JA, Tombes RM.

Gene. 2020 Mar 9:144567. doi: 10.1016/j.gene.2020.144567. [Epub ahead of print]

Monday, March 16, 2020 - 09:51
Shift Pharmaceuticals Orphan Drug: Morpholino for Spinal Muscular Atrophy

Shift Pharmaceuticals receives an Orphan Drug designation from the FDA for their Morpholino to treat Spinal Muscular Atrophy.

Monday, March 9, 2020 - 16:28
Golodirsen: First Approval. Morpholino drug for DMD (exon 53 skipper)

Golodirsen: First Approval.
Heo YA.
Drugs. 2020 Feb 6. doi: 10.1007/s40265-020-01267-2. [Epub ahead of print] Review.

This is an FDA-approved Morpholino drug that causes skipping of exon 53 of human dystrophin, used for the treatment of Duchenne muscular dystrophy.

Friday, February 7, 2020 - 14:46
Available fluorochromes attached to Morpholinos

I like carboxyfluorescein. It is bright, it doesn’t alter how the oligo behaves, and most labs already have a fluorescein cube (filters and dichroic mirror) for their fluorescent microscopes. The down side is that fluorescein photobleaches, so you should minimize its exposure to intense light and only observe it with the microscope when you are ready to take pictures and turn off the lamp soon. Carboxyfluorescein emits green.

Wednesday, January 8, 2020 - 07:40
A reversible RNA on-switch using a Vivo-Morpholino to controls gene expression of AAV-delivered therapeutics in vivo

Zhong G, Wang H, He W, Li Y, Mou H, Tickner ZJ, Tran MH, Ou T, Yin Y, Diao H, Farzan M. A reversible RNA on-switch that controls gene expression of AAV-delivered therapeutics in vivo. Nat Biotechnol. 2019;[Epub ahead print] doi:10.1038/s41587-019-0357-y
Vivo-Morpholino used to control activity of an engineered ribozyme

Press release:

Monday, December 23, 2019 - 13:27