From base editing to RNA editing (3)

By: James V. Kohl | Published on: October 31, 2017

Summary: Claims about spontaneous deamination fail to link energy-dependent changes from base editing to RNA-mediated DNA repair of damage caused by the virus-driven degradation of messenger RNA.
Highly efficient RNA-guided base editing in mouse embryos 27 February 2017
They reported the use of RNA-programmable deaminases to make various animal models with single amino-acid substitutions.They linked the single amino acid substitutions from the correction of nonsense mutations in the future to the correction of genetic defects in human embryos.
Reported as: An Efficient Single-Nucleotide-Editing CRISPR

“We showed here for the first time that programmable deaminases efficiently induced base substitutions in animal embryos, producing mutant mice with disease phenotypes,” remarked senior study investigator Jin-Soo Kim, Ph.D., director of the Center for Genome Engineering at IBS. “This is a proof-of-principle experiment. The next goal is to correct a genetic defect in animals. Ultimately, this technique may allow gene correction in human embryos.”

Their technique linked base editing to naturally occurring energy-dependent gene editing in human embyos.  These researchers also inadvertently linked what is known about the pheromone-controlled physiology of reproduction from microbes to human populations outside the context of mutation-driven evolution.
They helped force other researchers to place their findings back into the context of “evolved” biodiversity after first linking evolution to the spontaneous deamination of cytosine. Claims about spontaneous deamination fail to link energy-dependent changes from base editing to RNA-mediated DNA repair of damage caused by the virus-driven degradation of messenger RNA.
Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage

The spontaneous deamination of cytosine is a major source of C•G to T•A transitions, which account for half of known human pathogenic point mutations. The ability to efficiently convert target A•T base pairs to G•C could therefore advance the study and treatment of genetic diseases. While the deamination of adenine yields inosine, which is treated as guanine by polymerases, no enzymes are known to deaminate adenine in DNA. Here we report adenine base editors (ABEs) that mediate conversion of A•T to G•C in genomic DNA. We evolved a tRNA adenosine deaminase to operate on DNA when fused to a catalytically impaired CRISPR-Cas9. Extensive directed evolution and protein engineering resulted in seventh-generation ABEs (e.g., ABE7.10), that convert target A•T to G•C base pairs efficiently (~50% in human cells) with very high product purity (typically ≥ 99.9%) and very low rates of indels (typically ≤ 0.1%). ABEs introduce point mutations more efficiently and cleanly than a current Cas9 nuclease-based method, induce less off-target genome modification than Cas9, and can install disease-correcting or disease-suppressing mutations in human cells. Together with our previous base editors, ABEs advance genome editing by enabling the direct, programmable introduction of all four transition mutations without double-stranded DNA cleavage.

After a brief look at what they attribute to spontaneous deamination, please see: How flu shot manufacturing forces influenza to mutate

“Now we can explain — at an atomic level — why egg-based vaccine production is causing problems,” said TSRI Research Associate Nicholas Wu, Ph.D., first author of the study, published recently in the journal PLOS Pathogens.

In this 2014 invited review of nutritional epigenetics I linked energy-dependent changes from atoms to ecosystems in all living genera via food energy and the pheromone-controlled physiology of reproduction.

Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems

The plausibility and ecological validity of Kohl’s Laws [of Biology] in the context of Darwin’s ‘conditions of life’ can be compared to theories about biologically-based cause and effect in the context of species diversity. In mammals, for example, the explanatory power of a model of ecological variation and biophysically constrained nutrient-dependent pheromone-controlled ecological adaptations became clear with companion papers published in 2013. See for review [30].

The companion papers [162-163] told a new short story of ecological adaptations. In the context of climate change and changes in diet, the story began with what probably was a nutrient-dependent base pair change and a variant epiallele [amino acid substitution] that arose in a human population in what is now central China.

30) Kohl, J. V., Nutrient–dependent / pheromone–controlled adaptive evolution: a model. Socioaffective Neuroscience & Psychology 2013, 3. doi: 10.3402/snp.v3i0.20553
162) Kamberov, Yana G.; Wang, S.; Tan, J.; Gerbault, P.; Wark, A.; Tan, L.; Yang, Y.; Li, S.; Tang, K.; Chen, H., et al., Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant. Cell 2013, 152 (4), 691-702. doi: 10.1016/j.cell.2013.01.016
163) Grossman, Sharon R.; Andersen, Kristian G.; Shlyakhter, I.; Tabrizi, S.; Winnicki, S.; Yen, A.; Park, Daniel J.; Griesemer, D.; Karlsson, Elinor K.; Wong, Sunny H., et al., Identifying Recent Adaptations in Large-Scale Genomic Data. Cell 2013, 152 (4), 703-713. doi: 10.1016/j.cell.2013.01.035
See again: How flu shot manufacturing forces influenza to mutate

The researchers say further studies are needed to investigate replacing the egg-based system. “Other methods are now being used and explored for production of vaccines in mammalian cells using cell-based methods and recombinant HA protein vaccines,” said Wilson.

“There’s a huge need for flu vaccine research,” added Wu.

There is a huge need for biologically uninformed theorists to address the fact that the flu virus does not mutate and evolve.
See: Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution

The major antigenic changes of the influenza virus are primarily caused by a single amino acid near the receptor binding site.

The energy-dependent physiology of pheromone-controlled reproduction in species from microbes to humans prevents the virus-driven degradation of messenger RNA that links mutations to all pathology. Only RNA-mediated amino acid substitutions have been linked from ecological variation to ecological adaptations. Claims that anything mutates and evolved are not based on the facts about cell type differentiation that are known to all serious scientists.
Those facts are included in the rules of this game: Cytosis: A Cell Biology Board Game

A board game taking place inside a human cell! Players compete to build enzymes, hormones and receptors and fend off attacking Viruses!


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