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Vivo-Morpholinos as switching molecules for virally-delivered targets in mice

The authors of this new paper use an engineered viral vector (AAV) to express a secreted antibody. They make a version where the antibody is out-of-frame and a Morpholino is used to skip an exon, bring the antibody in-frame and switch on its functional expression; the target is a payload of the AAV and the switching molecule is the Morpholino. This use of Morpholinos as switching molecules in engineered systems has great therapeutic potential. In the same paper, they controlled the expression of their AAV cargo with a Vivo-Morpholino after delivery into a mouse.

Wednesday, August 10, 2022 - 12:14
Head-to-head comparisons, Morpholinos and Phosphorothioates

Single Stranded Fully Modified-Phosphorothioate Oligonucleotides can Induce Structured Nuclear Inclusions, Alter Nuclear Protein Localization and Disturb the Transcriptome In Vitro.

Flynn LL, Li R, Pitout IL, Aung-Htut MT, Larcher LM, Cooper JAL, Greer KL, Hubbard A, Griffiths L, Bond CS, Wilton SD, Fox AH, Fletcher S.

Front Genet. 2022;13:791416. doi:10.3389/fgene.2022.791416

Tuesday, April 19, 2022 - 10:15
Adverse Drug Reactions and Toxicity of the FDA-approved Antisense Oligonucleotide Drugs

Adverse Drug Reactions and Toxicity of the FDA-approved Antisense Oligonucleotide Drugs.
Alhamadani F, Zhang K, Parikh R, Wu H, Rasmussen TP, Bahal R, Zhong XB, Manautou JE. Drug Metab Dispos. 2022 Feb 27:DMD-MR-2021-000418. doi:10.1124/dmd.121.000418. Online ahead of print.

Thursday, March 24, 2022 - 14:08
Pharmacol & Tox of FDA-approved antisense

Absorption, distribution, metabolism, and excretion of FDA-approved antisense oligonucleotide drugs.
Migliorati JM, Liu S, Liu A, Gogate A, Nair S, Bahal R, Rasmussen TP, Manautou JE PhD, Zhong XB. Drug Metab Dispos. 2022 Feb 27:DMD-MR-2021-000417. doi: 10.1124/dmd.121.000417.

Tuesday, March 1, 2022 - 14:34
Electroporation protocol: Amaxa 4D X unit nucleofector system

Goossens R, Aartsma-Rus A. In Vitro Delivery of PMOs in Myoblasts by Electroporation. Methods Mol Biol. 2022;2434:191-205. doi: 10.1007/978-1-0716-2010-6_12.

Tuesday, March 1, 2022 - 08:50
Analysis of an apparent mutant/morphant disagreement

Barthelson K, Baer L, Dong Y, Hand M, Pujic Z, Newman M, Goodhill GJ, Richards RI, Pederson SM, Lardelli M. Zebrafish Chromosome 14 Gene Differential Expression in the fmr1 (h u2787) Model of Fragile X Syndrome. Front Genet. 2021 May 31;12:625466. doi: 10.3389/fgene.2021.625466. eCollection 2021.

Interesting analysis of an apparent mutant/morphant disagreement finding no genetic compensation experimentally.

Tuesday, February 8, 2022 - 14:24
Generating Zebrafish RNA-Less Mutant Alleles by Deleting Gene Promoters with CRISPR/Cas9

A frameshift mutation did not phenocopy the corresponding Morpholino. To avoid transcriptional adaptation (genetic compensation), the authors made mutants with deleted promoters, eliminating the NMD transcript that would trigger transcriptional adaptation.

Thursday, December 16, 2021 - 10:11
N=1 clinical trials (paper)

Preparing n-of-1 Antisense Oligonucleotide Treatments for Rare Neurological Diseases in Europe: Genetic, Regulatory, and Ethical Perspectives.
Synofzik M, van Roon-Mom WMC, Marckmann G, van Duyvenvoorde HA, Graessner H, Schüle R, Aartsma-Rus A. Nucleic Acid Ther. 2021 Sep 29. doi: 10.1089/nat.2021.0039. Online ahead of print.

Friday, October 1, 2021 - 09:29
Chemistry of Peptide-Oligonucleotide Conjugates: A Review

It appears CPP are becoming a hot topic for reviews. This is a nice open-access example.

Klabenkova K, Fokina A, Stetsenko D. Chemistry of Peptide-Oligonucleotide Conjugates: A Review. Molecules. 2021; 26(17):5420.

Friday, September 10, 2021 - 10:43
Review: Genotype-Phenotype Relationships in the Context of Transcriptional Adaptation and Genetic Robustness

Genotype-Phenotype Relationships in the Context of Transcriptional Adaptation and Genetic Robustness.
Jakutis G, Stainier DYR. Annu Rev Genet. 2021 Jul 27. doi: 10.1146/annurev-genet-071719-020342. Online ahead of print.

Wednesday, July 28, 2021 - 09:40