CRISPR Could Be Causing Extensive Mutations And Genetic Damage After All

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.

"We found that changes in the DNA have been seriously underestimated before now."

It's not the first time scientists have raised alarm about the potential pitfalls of CRISPR.

In May last year, a team  made headlines when they announced the genetic editing toolkit could introduce hundreds of off-target mutations to the genome.

Those claims were later retracted when the scientists involved in the original study were unable to replicate their own results, but since then other research has also suggested CRISPR could cause dangerous side effects.

To investigate these kinds of possibilities further, the researchers examined the effects of the technique on mouse stem cells and human retinal epithelial cells.

"My initial experiment used CRISPR/Cas9 as a tool to study gene activity, however it became clear that something unexpected was happening," says the first author of the new study.

"Once we realised the extent of the genetic rearrangements we studied it systematically, looking at different genes and different therapeutically relevant cell lines, and showed that the CRISPR/Cas9 effects held true."

Those effects included large deletions or mutations that happened even several thousand DNA bases (aka kilobases) away from the target site where CRISPR/Cas9 was used to make the edit.

Not only could such significant mutations of the DNA code have potentially harmful effects – by disrupting healthy gene and cellular functioning – but the researchers warn that standard DNA genotyping assays may not ordinarily pick up on these mistakes.

In the worst-case scenario, if such mangled edits were introduced into humans in a CRISPR/Cas9 treatment, important genes might end up being switched on or off, which could make for potentially serious health consequences.

"In the clinical context of editing many billions of cells, the multitude of different mutations generated makes it likely that one or more edited cells in each protocol would be endowed with an important pathogenic lesion," the authors write.

"Such lesions may constitute a first carcinogenic 'hit' in stem cells and progenitors, which have a long replicative lifespan and may become neoplastic [promoting abnormal growths] with time."

If such unforeseen side effects can indeed be introduced by using CRISPR/Cas9 to snip at the genome, the researchers say it's imperative for future clinical applications to address the risks.
And it's likely a lot more research will be needed to find out whether it's possible to prevent such editing errors from arising.

"It is important that anyone thinking of using this technology for gene therapy proceeds with caution," the author says "and looks very carefully to check for possible harmful effects."

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Cause of fatal disease that turns babies' lips, skin blue identified

Scientists using gen-editing tool. CRISPR/ Cas9 have identified the cause -- and a potential treatment -- of a fatal respiratory disorder newborn infants that turns their lips and skin blue.

The team used CRISPR/Cas9 to generate mice that mimic the mostly untreatable disorder called Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV). 

The model allowed researchers in the US to pinpoint the ailment's cause and develop a potential and desperately needed nano-particle-based treatment.

ACDMPV usually strikes infants within a month of birth. The disease starves the pulmonary system of oxygen after the lung's blood vessels do not form properly during organ development.

The lack of tiny blood vessels called alveolar capillaries causes hypoxia, inflammation and death, researchers said.

"There are no effective treatments other than a lung transplant, so the need for new therapeutics is urgent," said a Dr.

"We identified a nano-particle therapeutic strategy to increase the number of alveolar capillaries and help preserve respiratory function for at least a subset of the babies with this congenital lung disease," said the lead researcher in the study.

The disease has long been linked to mutations in the FOXF1 gene, an important regulator of embryonic lung development.

The remaining mystery until this study is precise microbiological processes that fuel ACDMPV, researchers said.

Researchers analysed genetic information from human ACDMPV cases to generate the first clinically relevant animal model of ACDMPV. They used CRISPR/ Cas9 to recreate human FOXF1 mutations in the mouse.

CRISPR-Cas9 allows precise gene editing by using an enzyme to cut out specific sections of a DNA sequence and reattaching the loose ends at a desired point to change a cell's genetic makeup.

Having clinically accurate mouse models of disease ACDMPV allowed the scientists to overcome a longtime hurdle to understanding how the disease develops, researchers said.

By studying protein-DNA interactions linked to the FOXF1 gene in pulmonary cells, researchers found a specific point mutation, which blocked molecular signalling to multiple downstream target genes involved in formation of pulmonary blood vessels.

The researchers theorised that treating newborn mice with a protein called STAT3 would stimulate blood vessel development in the lungs.

Researchers turned to nano-particle technology to deliver a STAT3 mini-gene to lungs of newborn mice. They created a novel formulation for what are known as polyethylenimine (PEI) nanoparticles.

The gelatin-like PEI nanoparticles can carry therapeutic genetic material to different parts of the body by administering them to patients intravenously.

Different formulations of PEI nanoparticles are currently being tested in clinical trials for adult cancer at other institutions, researchers said.

THIS IS ONLY FOR INFORMATION, ALWAYS CONSULT YOU PHYSICIAN BEFORE HAVING ANY PARTICULAR FOOD/ MEDICATION/EXERCISE/OTHER REMEDIES.                                    PS- THOSE INTERESTED IN RECIPES ARE FREE TO  VIEW MY BLOG-                                                                                           https://gseasyrecipes.blogspot.com/                                                                                                                                                FOR INFO ABOUT KNEE REPLACEMENT, YOU CAN VIEW MY BLOG-                                                  https:// kneereplacement-stickclub.blogspot.com/                                                                      FOR CROCHET DESIGNS                                                                                                                                                                                     https://gscrochetdesigns.blogspot.com