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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.

https://www.frontiersin.org/articles/10.3389/fgene.2021.625466/full

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.
https://pubmed.ncbi.nlm.nih.gov/34591693/

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. https://doi.org/10.3390/molecules26175420
https://www.mdpi.com/1420-3049/26/17/5420

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.
https://www.annualreviews.org/doi/pdf/10.1146/annurev-genet-071719-020342

Wednesday, July 28, 2021 - 09:40
Paper: Induction of cryptic pre-mRNA splice-switching by antisense oligonucleotide

Mostly phosphorothioate work

Ham KA, Keegan NP, McIntosh CS, Aung-Htut MT, Zaw K, Greer K, Fletcher Sue, Wilton SD. Induction of cryptic pre-mRNA splice-switching by antisense oligonucleotides. Sci Rep. 2021;11(1):15137 doi:10.1038/s41598-021-94639-x
https://www.nature.com/articles/s41598-021-94639-x

Friday, July 23, 2021 - 14:22
Genetic compensation in soybean (no Morpholino)

Genetic compensation in soybean: I am putting this in the blog as an example of an organism distant from zebrafish which is also compensating for mutation.

Friday, July 16, 2021 - 14:42
Nice introduction to splice-modification therapy from OTS

From the Oligonucleotide Therapeutics Society: "Can Oligonucleotides Target RNA Splicing to Treat Disease?"
https://www.oligotherapeutics.org/can-oligonucleotides-target-rna-splici...

Wednesday, June 23, 2021 - 09:41
Mutant-morphant mismatch but no genetic compensation

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

https://www.frontiersin.org/articles/10.3389/fgene.2021.625466/full

Friday, June 18, 2021 - 08:14
Morphant vs mutant: "...this knockout line is deemed unsuitable for our study."

Here’s a nice description of why, in this study, morphants are preferable to mutants.

Friday, June 11, 2021 - 11:53

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