Genome engineers made more than 13,000 CRISPR edits in a single cell – A team at George Church’s Harvard lab wants to redesign species with large-scale DNA changes. By Antonio Regalado March 26, 2019 @ Invitation by Facebook Group to participate at the “INTERNATIONAL CONFERENCE ON FUNCTIONAL NANOMATERIALS AND NANODEVICES” (#NANOMAT2019), to be held 11-13 September 2019 in Prague, Czech Republic. #time @ www.google.com #history #person #country #people #analysis

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Pathol Res Pract. 2012 Jul 15;208(7):377-81. doi: 10.1016/j.prp.2012.04.006. Epub 2012 Jun 8.

The influence of physical activity in the progression of experimental lung cancer in mice

Renato Batista Paceli 1Rodrigo Nunes CalCarlos Henrique Ferreira dos SantosJosé Antonio CordeiroCassiano Merussi NeivaKazuo Kawano NagaminePatrícia Maluf Cury


Impact_Fator-wise_Top100Science_Journals

GRUPO_AF1GROUP AFA1 – Aerobic Physical Activity – Atividade Física Aeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto

GRUPO AFAN 1GROUP AFAN1 – Anaerobic Physical ActivityAtividade Física Anaeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto

GRUPO_AF2GROUP AFA2 – Aerobic Physical ActivityAtividade Física Aeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto

GRUPO AFAN 2GROUP AFAN 2 – Anaerobic Physical ActivityAtividade Física Anaeróbia´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto

Slides – mestrado´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto

CARCINÓGENO DMBA EM MODELOS EXPERIMENTAIS

DMBA CARCINOGEN IN EXPERIMENTAL MODELS

Avaliação da influência da atividade física aeróbia e anaeróbia na progressão do câncer de pulmão experimental – Summary – Resumo´´My´´ Dissertation Faculty of Medicine of Sao Jose do Rio Preto

https://pubmed.ncbi.nlm.nih.gov/22683274/

Abstract

Lung cancer is one of the most incident neoplasms in the world, representing the main cause of mortality for cancer. Many epidemiologic studies have suggested that physical activity may reduce the risk of lung cancer, other works evaluate the effectiveness of the use of the physical activity in the suppression, remission and reduction of the recurrence of tumors. The aim of this study was to evaluate the effects of aerobic and anaerobic physical activity in the development and the progression of lung cancer. Lung tumors were induced with a dose of 3mg of urethane/kg, in 67 male Balb – C type mice, divided in three groups: group 1_24 mice treated with urethane and without physical activity; group 2_25 mice with urethane and subjected to aerobic swimming free exercise; group 3_18 mice with urethane, subjected to anaerobic swimming exercise with gradual loading 5-20% of body weight. All the animals were sacrificed after 20 weeks, and lung lesions were analyzed. The median number of lesions (nodules and hyperplasia) was 3.0 for group 1, 2.0 for group 2 and 1.5-3 (p=0.052). When comparing only the presence or absence of lesion, there was a decrease in the number of lesions in group 3 as compared with group 1 (p=0.03) but not in relation to group 2. There were no metastases or other changes in other organs. The anaerobic physical activity, but not aerobic, diminishes the incidence of experimental lung tumors.

Copyright © 2012 Elsevier GmbH. All rights reserved.

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Wolfgang Kumm | AP images

Rewriting Life

Genome engineers made more than 13,000 CRISPR edits in a single cell

A team at George Church’s Harvard lab wants to redesign species with large-scale DNA changes.

Since its invention, CRISPR has let scientists introduce DNA changes at specific locations in a genome. Often these precise changes are made one at a time.

Perhaps not for much longer. A team at Harvard University says it has used the technique to make 13,200 genetic alterations to a single cell, a record for the gene-editing technology.

The group, led by gene technologist George Church, wants to rewrite genomes at a far larger scale than has currently been possible, something it says could ultimately lead to the “radical redesign” of species—even humans.

Large-scale gene editing of this sort has been tried before. In 2017, an Australian team led by Paul Thomas peppered the Y chromosome of mice with edits and succeeded in blasting it out of existence. That strategy is being eyed as a potential treatment for Down syndrome, a genetic disorder caused by an extra chromosome.

To set the new gene-editing record, team members Oscar Castanon and Cory Smith aimed CRISPR at a type of DNA sequence called a LINE-1, a mysterious repetitive element found littered across the human genome. These genetic elements, which are able to copy themselves, are estimated to account for about 17% of our genome.

Because CRISPR cuts open the double helix, making too many edits at once will kill a cell. This danger has limited past attempts at large-scale editing. Geoff Faulkner, of the University of Queensland in Australia, says in 2016 he tried knocking out LINE elements in 500 mouse embryos, hoping to see if this would affect mouse behavior. But no such mice survived to reproduce.

To avoid that problem, the Harvard team instead adapted a variation of CRISPR called a base editor that avoids cutting DNA and instead replaces one genetic letter with another—say, turning a C into a T.

According to their paper, posted in March to the preprint website BioRxiv, the team was able to make over 13,000 changes at once in some cells without destroying them.

“They found a way to do the experiment without causing gross genome-wide instability,” Faulkner says.

Other scientists were less impressed, saying the work isn’t the “enabling” step for large-scale genome editing it is advertised to be. Gaetan Burgio, of the Australian National University, called the idea that the technique will lead to a radical redesign of species “way exaggerated.”

Church, however, sees large-scale editing as a way to clean up genomes by removing the genetic junk they contain. In 2015, for example, the lab zapped all 62 copies of a retrovirus that lurks inside the genomes of pigs. Such viruses can reactivate, so creating pigs without them is a safety step toward pig-to-human organ transplants.

A company spun out of the lab, eGenesis , is already creating pigs with scores of edits so their organs can be tolerated by human transplant recipients.

Church says his eventual objective is to create supplies of human organs or tissues whose genomes are revised so they are immune to all viruses. That process, called recoding, would involve about 9,811 precise genetic modifications, according to the team. Church says the lab has started the process of recoding supplies of his own cells in the lab. “These are intended to be safe … and universal stem cells,” he says.

MIT Technology Review © 2019

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