NHEJ disruption and HDR correction?

By: James V. Kohl | Published on: June 14, 2018

International Workshop “Targeting RNA world”

Dear colleagues!
Scientists of the Institute of Chemical Biology and Fundamental Medicine SB RAS cordially invites you to attend International Workshop “Targeting RNA world” in the frame of the project of Russian Scientific Foundation “New generation of RNA-targeting oligonucleotide derivatives as a platform for designing innovative therapeutics” (no. 14-44-00068). Workshop is being held in Park Inn by Radisson Pulkovskaya Hotel & Conference Centre St Petersburg, Saint-Petersburg, Russia, September 2-7 2018.
We will discuss all aspects of RNA targeting with the purpose of target validation, oligonucleotide modification, functionalization and delivery, molecular modeling of RNA/oligonucleotide and RNA/protein complexes, development of RNA-targeting drugs and translational studies.

It is time to see RNA-mediated.com since every aspect of biophysically constrained biodiversity is energy-dependent and microRNA-mediated in the context of claims made in 1994 by Eugene Daev.  [Pheromonal regulation of genetic processes: research on the house mouse (Mus musculus L.)].
His claims can readily be linked from the claims in the molecular epigenetics section from this 1996 Hormones and Behavior review From Fertilization to Adult Sexual Behavior to sympatric speciation and all biodiversity via the quantized energy-dependent creation of microRNAs (microRNA biogenesis).

See also: An interplay of miRNA abundance and target site architecture determines miRNA activity and specificity

…for some target site architectures, elevated miRNA levels can compensate for a lack of complementarity outside the seed. Thus, some target sites require higher miRNA concentration for silencing than others, contrasting with a traditional binary distinction between functional and non-functional sites. We conclude that changing miRNA concentrations can alter cellular miRNA target repertoires. This diversifies possible biological outcomes of miRNA-mediated gene regulation and stresses the importance of target validation under physiological conditions to understand miRNA functions in vivo.

See also: The Emerging Role of RNA as a Therapeutic Target for Small Molecules (2016)
This review highlights advances and successes in approaches to targeting RNA with diverse small molecules, and the potential for these technologies to pave the way to new types of RNA-targeted therapeutics.
This 2014 invited review of nutritional epigenetics highlighted the advances I learned about after attending a conference presentation on microRNAs during the 2012 Society for Neuroscience annual meeting in New Orleans, LA USA. It was published in ~60 different languages in April 2018 as: Nutrient-dependent Pheromone-Controlled Ecological Adaptations: From Angstroms to Ecosystems. (As expected, after  more than one month, no one has commented on this publication at the journal site.) Pseudoscientists and other theorists are forced to ignore paradigm shifts.
See also:  Measuring RNA-Ligand Interactions with Microscale Thermophoresis (2018)

Here, we demonstrate how MST can be used to study a range of biologically relevant RNA interactions, including peptide-RNA interactions, RNA-small molecule interactions, and displacement of an RNA-bound peptide by a small molecule.

The biologically relevant RNA interactions link the creation of ATP synthase from the creation of ATP and the creation of microRNAs to the peptide-RNA interactions and displacement of RNA-bound amino acid substitutions via the quantized energy as information-dependent microRNA-mediated cell type differentiation that links fixation of amino acid substitutions to cell type differentiation in the context of the physiology of pheromone-controlled reproduction.
See for comparison: A serious new hurdle for CRISPR: Edited cells might cause cancer, two studies find

…the Novartis team showed, p53 inactivation seems to be necessary for both NHEJ disruption and HDR correction. (Novartis’ Kaykas said he could not speak to a reporter without clearance from the company’s communications office.) That could be an issue for therapies using CRISPR’d stem cells: The same dysfunctional p53 that allows CRISPR to work its magic also makes cells likely to become cancerous.

Re: NHEJ disruption and HDR correction.
With minimal investigation of what is known to serious scientists about biophysically constrained viral latency, you can find the these terms are used to obfuscate cause and effect in attempts to avoid litigation because the researchers should have known what might happen if the “death gene” was inactivated by the virus used  in gene editing.
See: Reduced expression of brain-enriched microRNAs in glioblastomas permits targeted regulation of a cell death gene

A single A to I conversion in the seed of miR-376a-5p, for example, redirects the edited miRNA to a new set of mRNA targets [25]. In deep sequencing libraries, this conversion is marked by the substitution of A with G.

See also: All About that Base (Meghan Trainor Parody) 12/10/14 and Energy as information and constrained endogenous RNA interference

Feedback loops link quantized energy as information to biophysically constrained RNA-mediated protein folding chemistry. Light induced energy-dependent changes link angstroms to ecosystems from classical physics to chemistry/chirality and to molecular epigenetics/autophagy. The National Microbiome Initiative links microbial quorum sensing to the physiology of reproduction via endogenous RNA interference and chromosomal rearrangements. The rearrangements link energy-dependent fixed amino acid substitutions to the Precision Medicine Initiative via genome wide inferences of natural selection. This detailed representation of energy-dependent natural selection for codon optimality links biologically- based cause and effect from G protein-coupled receptors to RNA-mediated amino acid substitutions and the functional structure of supercoiled DNA. Energy-dependent polycombic ecological adaptations are manifested in supercoiled DNA. Chromosomal inheritance links the adaptations from morphological phenotypes to healthy longevity via behavioral phenotypes. For contrast, virus-driven energy theft is the link from messenger RNA degradation to negative supercoiling, constraint breaking mutations, and hecatombic evolution. The viral hecatomb links transgenerational epigenetic inheritance from archaea to Zika virus-damaged DNA, which typically is repaired by endogenous RNA interference and fixation of RNA-mediated amino acid substitutions in organized genomes.

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