Scientists propose efficiency ‘rules’ for enhancing use of new gene editing technology

Scientists propose efficiency ‘rules’ for enhancing use of new gene editing technology

Johns Hopkins scientists have developed a streamlined method and accompanying efficiency “rules” for introducing new DNA sequences into cells after using the gene-cutting tool known as CRISPR. The scientists say the method, which they based on tests with mouse embryos and thousands of human cells, could improve consistency and efficiency of genome editing.

The new method and its development are described online in the Nov. 28 in the Proceedings of the National Academy of Sciences.
“CRISPR is a tool to help scientists modify the genome, predict the outcome of certain traits and study them, but the tool itself only creates breaks in the genome. It does not control how a new DNA sequence is inserted into the genome,” says Geraldine Seydoux, Ph.D., the Huntington Sheldon Professor in Medical Discovery in the Department of Molecular Biology and Genetics and vice dean for basic research at the Johns Hopkins University School of Medicine, and an investigator with the Howard Hughes Medical Institute.
“We set out to study how cells repair breaks induced by CRISPR with the goal of using the cell’s natural DNA repair process to introduce new sequences in the genome. We were surprised to find that cells will readily copy sequences from foreign DNA to repair DNA breaks, as long as the foreign DNAs are linear,” Seydoux adds. “By studying how foreign DNA fragments are copied during the repair process, we came up with some simple rules to make genome editing as efficient as possible, optimize the tool, and do so with confidence.”
CRISPR, which stands for clustered regularly interspaced short palindromic repeat, has gained popularity among scientists in the last five years as a tool to efficiently cut DNA. It was adapted for use in mammalian cells from a natural viral defense process in bacterial cells that involves creating lethal cuts in viral DNA. Essentially, the tool is a streamlined set of molecular “scissors.”
The prevailing belief, among scientists, is that cells repair DNA breaks by inserting a random set of nucleotides, the chemical building blocks of DNA. This usually destroys any gene that’s located at the spot where the DNA is broken.
It’s also well known to scientists that, occasionally, cells use a different source—a sequence from another piece of DNA, or “donor” DNA—to seal the break in DNA. However, the new “donor” sequence cannot be inserted by itself into an empty space in the genome.
Instead, the new donor DNA needs a kind of tape at each end to help it stick within the gap made by the cut. Scientists refer to this tape as the “homology” arms of the donor DNA.

The new method and its development are described online in the Nov. 28 in the Proceedings of the National Academy of Sciences.
“CRISPR is a tool to help scientists modify the genome, predict the outcome of certain traits and study them, but the tool itself only creates breaks in the genome. It does not control how a new DNA sequence is inserted into the genome,” says Geraldine Seydoux, Ph.D., the Huntington Sheldon Professor in Medical Discovery in the Department of Molecular Biology and Genetics and vice dean for basic research at the Johns Hopkins University School of Medicine, and an investigator with the Howard Hughes Medical Institute.
“We set out to study how cells repair breaks induced by CRISPR with the goal of using the cell’s natural DNA repair process to introduce new sequences in the genome. We were surprised to find that cells will readily copy sequences from foreign DNA to repair DNA breaks, as long as the foreign DNAs are linear,” Seydoux adds. “By studying how foreign DNA fragments are copied during the repair process, we came up with some simple rules to make genome editing as efficient as possible, optimize the tool, and do so with confidence.”
CRISPR, which stands for clustered regularly interspaced short palindromic repeat, has gained popularity among scientists in the last five years as a tool to efficiently cut DNA. It was adapted for use in mammalian cells from a natural viral defense process in bacterial cells that involves creating lethal cuts in viral DNA. Essentially, the tool is a streamlined set of molecular “scissors.”
The prevailing belief, among scientists, is that cells repair DNA breaks by inserting a random set of nucleotides, the chemical building blocks of DNA. This usually destroys any gene that’s located at the spot where the DNA is broken.
It’s also well known to scientists that, occasionally, cells use a different source—a sequence from another piece of DNA, or “donor” DNA—to seal the break in DNA. However, the new “donor” sequence cannot be inserted by itself into an empty space in the genome.
Instead, the new donor DNA needs a kind of tape at each end to help it stick within the gap made by the cut. Scientists refer to this tape as the “homology” arms of the donor DNA.

Source:https://phys.org/news/2017-12-scientists-efficiency-gene-technology.html

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