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September 15, 2010 (Vol. 30, No. 16)

Re-Editing the Genome for Mistakes of Nature

Cellectis Says It Can Cut and Paste DNA Sequences with Its "Molecular Scissors"

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    Cellectis has developed various genome engineering applications that are based on meganucleases. Its proprietary process involves introducing a meganuclease that is specific to the targeted site into the cell and inserting a gene with the attributes required to stimulate homologous recombination. The meganuclease breaks the DNA molecule, and the homologous recombination system corrects this break by taking as a model the gene introduced at the same time as the meganuclease.

    When a meganuclease enters a cell, it can cut out a mutation, repair the cell, and re-edit the genome for the spelling mistakes of nature, says André Choulika, Ph.D., founder of Cellectis, who has served as CEO since the company’s inception. “It can unlock or restore DNA’s potential.”

    The main biotechnology tools developed by Cellectis are based on the properties of meganucleases, natural “molecular scissors” that can cut DNA at a precise site specific to each meganuclease, the company reports. It claims that once the cut has been made, it is possible to remove, integrate, or substitute a portion of DNA with the same degree of precision.

    “These DNA scissors induce cutting and pasting of DNA sequences at specific locations in living cells, offering powerful applications and potential in the fields of human therapeutics, agriculture, and biofuels,” according to Dr. Choulika. “The genome-engineering technology based on meganucleases can potentially be applied to any living organism.”

    Having worked with meganucleases since 1988 at the Institut Pasteur in Paris, Dr. Choulika is a pioneer in the field and the author of numerous patents on the use of meganucleases in vivo. His research team discovered meganucleases—enzymes that promote DNA transfer—in Saccharomyces cerevisiae.

    The researchers moved on to retroviruses and DNA recombination in mice. When they experimented with meganucleases in mammalian cells, they incorporated the recognition site of a meganuclease they were working on into a retrovirus, tried the DNA scissors out on infected cells, and discovered that the retrovirus disappeared.

    “We could remove the virus from a cell, which was a total paradigm shift at the time in terms of our way of thinking about antivirals,” Dr. Choulika says.

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