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Nanoblades Are Another Delivery Option for Gene Editing into Live Organisms

Targeted genome editing tools, such as meganucleases (MGN), zinc-finger nucleases (ZFN), transcription activator-like effector nucleases (TALENs) and more recently the clustered regularly interspaced short palindromic repeats (CRISPR) have revolutionized most biomedical research fields. Such tools allow to precisely edit the genome of eukaryotic cells by inducing double-stranded DNA (dsDNA) breaks at specific loci. Relying on the cell endogenous repair pathways, dsDNA breaks can then be repaired by non-homologous end-joining (NHEJ) or homology-directed repair (HDR) allowing the removal or insertion of new genetic information at a desired locus.

Among the above-mentioned tools, CRISPR-Cas9 is currently the most simple and versatile method for genome engineering. Indeed, in the two-component system, the bacterial-derived nuclease Cas9 (for CRISPR-associated protein 9) associates with a single-guide RNA (sgRNA) to target a complementary DNA sequence and induce a dsDNA break. Therefore, by the simple modification of the sgRNA sequence, users can specify the genomic locus to be targeted. Consistent with the great promises of CRISPR-Cas9 for genome engineering and gene therapy, considerable efforts have been made in developing efficient tools to deliver the Cas9 and the sgRNA into target cells ex vivo either by transfection of plasmids coding for the nucleases, transduction with viral-derived vectors coding for the nucleases or by direct injection or electroporation of Cas9-sgRNA complexes into cells.

Researchers have designed Nanoblades, a protein-delivery vector based on friend murine leukemia virus (MLV) that allows the transfer of Cas9-sgRNA ribonucleoproteins (RNPs) to cell lines and primary cells in vitro and in vivo. Nanoblades deliver the ribonucleoprotein cargo in a transient and rapid manner without delivering a transgene and can mediate knock-in in cell lines when complexed with a repair template. Nanoblades can also be programmed with modified Cas9 proteins to mediate transient transcriptional activation of targeted genes.

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Cryptic mutation is cautionary tale for crop gene editing

Even in this “age of the genome,” much about genes remains shrouded in mystery. This is especially true for “cryptic mutations”—mutated genes that are hidden, and have unexpected effects on traits that are only revealed when combined with other mutations. Learning from one infamous cryptic mutation in particular, researchers from CSHL share important lessons for breeding or gene editing in crops.

This story starts with the Campbell Soup Company and a field of tomatoes in the mid 20th century. One particular tomato plant had an unexpected beneficial trait: the fruits separated from the vine right where the green cap and stem touch the rest of the fruit. It turned out that this spontaneous natural mutant was ideal for large-scale production.

Other tomato varieties would break away at a joint-like nub in their fruit stems, leaving the pointed green caps on the fruits. With stems still present, these capped tomatoes would get easily bruised in the machine-picking process or end up puncturing one another in transit. However, the lucky Campbell Soup mutant didn’t have these problems. It was jointless, and perfect for a growing, automated industry. Unsurprisingly, breeders called the that drives this beneficial trait jointless-2 (j2).

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Michael Phelps: The ‘natural’ transhuman athlete

#Interesting #opinion This was brought up a decade ago, yet he was never asked to alter his genetics to make it fair for others. Is the current case one of discrimination? The recent work on the Chinese CRISPER babies showed that it augmented their ability. Will CRISPER babies also have in the future to “Change Their Genetics” to compete in sports if deemed unfair advantage?

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How Animals Code Their Kids for Survival

It turns out the capacity for offspring to benefit from their parents’ experiences doesn’t just happen with fish. Munday tells me about Daphnia, often called water fleas, that are found in freshwater lakes, ponds, and puddles. The tiny crustacean can hatch with either a round head or a pointed head. If it shares the water with predators such as fish or midges or other insects, spikes and spines help lessen the likelihood of being eaten. For many species of juvenile water flea…


Insights into epigenetics and inheritance show that some organisms can adapt to a changing world.

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PROFESSOR DAVID SINCLAIR | Can Humans Live For 1000 Years? | Modern Wisdom Podcast #066

David Sinclair is a Professor in the Department of Genetics at Harvard Medical School and co-Director of the Paul Glenn Centre for the Biological Mechanisms of Ageing.

Today we hear from a scientist at the cutting edge of longevity research as Professor Sinclair gives us a fascinating insight into the world of anti-ageing.

Expect to learn how and why we age, why stabilising the epigenetic landscape may enable a human to live for 1000 years, exactly what tactics Professor Sinclair is using himself to try and extend his life and how fasting, Sirtuins and NAD can be used to promote health and reduce diseases.

Extra Stuff:
David’s New Book — http://lifespanbook.com/
Follow David on Twitter — https://twitter.com/davidasinclair
Inside Tracker — https:// www.insidetracker.com
Recommended Books — https://www.amazon.co.uk/shop/chriswillx

Listen to all episodes online. Search “Modern Wisdom” on any Podcast App or click here:
iTunes: https://apple.co/2MNqIgw
Spotify: https://spoti.fi/2LSimPn
Stitcher: https://www.stitcher.com/podcast/modern-wisdom

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