CRISPR can be a blessing or a curse! Caution is advised! Double checking of innovations is needed! No rush please!
"... To get the cell to use homology-directed repair, the researchers recently began using a molecule called AZD7648, which blocks fast repair and forces the cell to use homology-directed repair. This approach is expected to accelerate the development of more efficient gene therapies. Initial studies with these new therapies have been good. Too good to be true, as it turned out.
A research group ... discovered that the use of AZD7648 has serious side effects. The study has been published in the journal Nature Biotechnology. ...
Extent of damage is large
The extent of the negative effects surprised the researchers. ...
The ETH researchers then analyzed the sequence of DNA building blocks not only around the edited site but also in the wider environment. They discovered these unwanted and catastrophic side effects caused by using AZD7648. ..."
From the abstract:
''The DNA-PKcs inhibitor AZD7648 enhances CRISPR–Cas9-directed homology-directed repair efficiencies, with potential for clinical utility, but its possible on-target consequences are unknown. We found that genome editing with AZD7648 causes frequent kilobase-scale and megabase-scale deletions, chromosome arm loss and translocations. These large-scale chromosomal alterations evade detection through typical genome editing assays, prompting caution in deploying AZD7648 and reinforcing the need to investigate multiple types of potential editing outcomes."
Crispr-Cas: die Balance finden zwischen Effizienz und Sicherheit (original news release in German) "ETH-Forschende decken eine gravierende Nebenwirkung bei einer Anwendung der Genschere Crispr-Cas auf. Ein Molekül, das den Vorgang effizienter machen soll, zerstört Bereiche des Genoms."
Fig. 2: AZD7648 increases the frequency of megabase-scale deletions, chromosome arm loss and translocations.
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