A new gene-editing system tackles complex diseases

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A new gene-editing system tackles complex diseases
Human BiologyDiseases And ConditionsPersonalized Medicine
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Current methods to model or correct mutations in live cells are inefficient, especially when multiplexing -- installing multiple point mutations simultaneously across the genome. Researchers have developed new, efficient genome editing tools called multiplexed orthogonal base editors (MOBEs) to install multiple point mutations at once.

Current methods to model or correct mutations in live cells are inefficient, especially when multiplexing -- installing multiple point mutations simultaneously across the genome. Researchers have developed new, efficient genome editing tools called multiplexed orthogonal base editors to install multiple point mutations at once.

One issue with using the genome in disease modeling is the sheer number of possible variations. If scientists were trying to determine which genetic mutations were responsible for heart disease, they could decode the genomes of a cohort that all had heart disease but the number of variations between any two people makes it very hard to determine which combination of variations causes the disease.

etions -- where the cell is not able to perfectly repair itself. Editing multiple genes in CRISPR-Cas9 multiples the risks. Cowan's MOBEs use RNA structures called aptamers -- small RNA loops that bind to specific proteins -- to recruit base-modifying enzymes to specific genomic locations enabling simultaneous editing of multiple sites with high efficiency and a lower incidence of crosstalk.

The study was a proof of principle to test the feasibility of the MOBE system, which has been granted a provisional patent. To test them even further, the team conducted several case studies with real diseases, including Kallmann syndrome, a rare hormonal disorder. Their experiments revealed that MOBE systems could be used to efficiently edit relevant cell lines of certain polygenic diseases.

Full list of authors: Quinn T. Cowan, Sifeng Gu, Wanjun Gu, Brodie L. Ranzau, Tatum S. Simonson, and Alexis C. Komor .Researchers have developed a novel genome editing technique known as NICER, which results in significantly fewer off-target mutations than CRISPR/Cas9 editing. The technique uses a different type of ...

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