Blogs

Overview of nucleic acid analogs, including which are approved as drugs.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469316/

Sun C, Shen L, Zhang Z, Xie X. Therapeutic Strategies for Duchenne Muscular Dystrophy: An Update. Genes. 2020;11:837. doi:10.3390/genes11080837
Open-access review article
https://www.mdpi.com/2073-4425/11/8/837

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.

Lim KH, Han Z, Jeon HY, Kach J, Jing E, Weyn-Vanhentenryck S, Downs M, Corrionero A, Oh R, Scharner J, Venkatesh A, Ji S, Liau G, Ticho B, Nash H, Aznarez I. Antisense oligonucleotide modulation of non-productive alternative splicing upregulates gene expression. Nat Commun. 2020;11(1):3501. doi:10.1038/s41467-020-17093-9

https://www.nature.com/articles/s41467-020-17093-9

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
https://www.mdpi.com/2077-0383/9/6/2004

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].
http://www.ncbi.nlm.nih.gov/pubmed/25620705

Forcing a terminal intron inclusion:
Shchelkunova A, Ermolinsky B, Boyle M, Mendez I, Lehker M, Martirosyan KS, Kazansky AV. Tuning of Alternative Splicing - Switch From Proto-Oncogene to Tumor Suppressor. Int J Biol Sci. 2013;9(1):45-54. doi:10.7150/ijbs.5194.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535533/

Blocking regulatory elements to increase intron retention:
Parra M, Yeo G, Conboy JG. Intron Retention Mechanisms That Regulate SF3B1 and Mitoferrin Gene Expression during Late Erythropoiesis. Blood. 2016;128:1200.
http://www.bloodjournal.org/content/128/22/1200

Long-term Safety & Efficacy of Golodirsen in Male Patients with Duchenne Muscular Dystrophy (DMD) Amenable to Exon 53 Skipping
https://mdaconference.org/node/936

PMO-based miRNA site blocking oligo (SBO) mediated utrophin upregulation in mdx mice, a therapeutic approach for Duchenne Muscular Dystrophy (DMD)
https://mdaconference.org/node/1000

Safety of eteplirsen in Duchenne Muscular Dystrophy post-Cardiac transplantation
https://mdaconference.org/node/913

Open-Label Evaluation of Eteplirsen in Male Patients With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping vs Untreated Control: PROMOVI Trial
https://mdaconference.org/node/1088

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. https://www.nippon-shinyaku.co.jp/file/download.php?file_id=2965

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]

https://www.sciencedirect.com/science/article/abs/pii/S0378111920302365

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

https://smauk.org.uk/blog/treatments-research/shift-pharmaceuticals-rece...

https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm...

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

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