Lifeboat Foundation

When CRISPR-Cas9 is used to edit genomes, off-target DNA damage is more common than previously thought.

A GREAT deal rides on the accuracy of the gene-editing tool known as CRISPR-Cas9. Since its discovery in 2012 it has become popular for tinkering with genomes of all kinds, thanks to its ability to make editing cheap and easy. Firms such as CRISPR Therapeutics, Intellia Therapeutics and Editas Medicine have been built on the idea that it could be used to develop treatments for human diseases. Editas, based in Cambridge, Massachusetts, announced this year that it would work on five new human medicines over the next five years.

In China the technology is already in clinical use. In Hangzhou Cancer Hospital, for example, CRISPR-Cas9 is being employed to engineer immune-system cells removed from patients with cancer of the oesophagus. The hope is that when the engineered cells are returned to a patient’s body, the editing will have improved their ability to attack tumours. More studies involving human beings are expected in other countries for the treatment of beta-thalassaemia, a blood disorder, and Leber’s congenital amaurosis, a form of blindness. Further ahead, there is hope that CRISPR-Cas9 will help treat diseases such as AIDS, cystic fibrosis, Huntington’s chorea and Duchenne muscular dystrophy.

Continue reading “The safety of CRISPR-Cas9 gene editing is being debated” »

Scientists like Dan Carlson are in high demand, thanks to recently discovered tools that enable them to tweak the DNA of all kinds of organisms.

Mitochondrial dysfunction is associated with many mitochondrial diseases, most of which are the result of dysfunctional mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial OXPHOS accounts for the generation of most of the cellular adenosine triphosphate (ATP) in a cell. The OXPHOS function largely depends on the coordinated expression of the proteins encoded by both nuclear and mitochondrial genomes. The human mitochondrial genome encodes for 13 polypeptides of the OXPHOS, and the nuclear genome encodes the remaining more than 85 polypeptides required for the assembly of OXPHOS system. Mitochondrial DNA (mtDNA) depletion impairs OXPHOS that leads to mtDNA depletion syndromes (MDSs)^{1, 2}. The MDSs are a heterogeneous group of disorders, characterized by low mtDNA levels in specific tissues. In different target organs, mtDNA depletion leads to specific pathological changes. MDS results from the genetic defects in the nuclear-encoded genes that participate in mtDNA replication, and mitochondrial nucleotide metabolism and nucleotide salvage pathway^{1, 4,5,6,7,8,9,10}. mtDNA depletion is also implicated in other human diseases such as mitochondrial diseases, cardiovascular^{11, 12}, diabetes^13,14,15, age-associated neurological disorders^16,17,18, and cancer^{19,20,21,22,23,24,25}.

A general decline in mitochondrial function has been extensively reported during aging^{26,27,28,29,30,31,32,33}. Furthermore, mitochondrial dysfunction is known to be a driving force underlying age-related human diseases^{16,17,18, 34,35,36}. A mouse that carries elevated mtDNA mutation is also shown to present signs of premature aging^{37, 38}. In addition to mutations in mtDNA, studies also suggest a decrease in mtDNA content and mitochondrial number with age^{27, 29, 32, 33, 39}. Notably, there is an age-related mtDNA depletion in a number of tissues^40,41,42. mtDNA depletion is also frequently observed among women with premature ovarian aging⁴³. Low mtDNA copy number is linked to frailty and, for a multiethnic population, is a predictor of all-cause mortality⁴⁴. A recent study revealed that humans on an average lose about four copies of mtDNA every ten years. This study also identified an association of decrease in mtDNA copy number with age-related physiological parameters³⁹.

To help define the role of mtDNA depletion in aging and various diseases, we created an inducible mouse expressing, in the polymerase domain of POLG1, a dominant-negative (DN) mutation that induces depletion of mtDNA in the whole animal. Interestingly, skin wrinkles and visual hair loss were among the earliest and most predominant phenotypic changes observed in these mice. In the present study, we demonstrate that mtDNA depletion-induced phenotypic changes can be reversed by restoration of mitochondrial function upon repletion of mtDNA.

https://paper.li/e-1437691924#/

In a newly released report, an influential UK ethics council concludes that editing human embryos is “morally permissible.”

“The DNA chaos that CRISPR unleashes has been ‘seriously underestimated,’” study author and geneticist Allan Bradley of U.K.’s Wellcome Sanger Center tells STAT. “This should be a wake-up call.”

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The Nuffield Council on Bioethics says changing the DNA of a human embryo could be ‘morally permissable’ if it is in the child’s best interests.

Ian Sample Science editor.

CRISPR has been heralded as one of the most important breakthroughs in modern science, but there could be a hidden and potentially dangerous side effect to the wonders of its genetic editing technology, a new study reveals.

A systematic investigation of CRISPR/Cas9 genome editing in mouse and human cells has discovered that the technique appears to frequently cause extensive mutations and genetic damage that the researchers say wouldn’t be detected by existing DNA tests.

“This is the first systematic assessment of unexpected events resulting from CRISPR/Cas9 editing in therapeutically relevant cells,” explains geneticist Allan Bradley from the Wellcome Sanger Institute in the UK.

Continue reading “BREAKING: CRISPR Could Be Causing Extensive Mutations And Genetic Damage After All” »

Project Recode may be the most ambitious science experiment of our time – genetically engineering humans to be virus-resistant.

Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute (MBI) at the National University of Singapore (NUS) and the FIRC Institute of Molecular Oncology (IFOM) in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification — by confining them to a defined geometric space for an extended period of time.

“Our breakthrough findings will usher in a new generation of stem cell technologies for tissue engineering and regenerative medicine that may overcome the negative effects of geonomic manipulation,” said Prof Shivashankar.